NM_007254.4:c.1029+2T>C

Variant names:

• chr19-49862369-A-G
• rs199919568
• NM_007254.4:c.1029+2T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Moderate PP5

The NM_007254.4(PNKP):​c.1029+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,280,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: PNKP NM_007254.4 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:25 U:4
• Conservation: PhyloP100: 3.19
• Publications: 12 publications found

Genes affected

PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

PNKP Gene-Disease associations (from GenCC):

• ataxia - oculomotor apraxia type 4

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P, Laboratory for Molecular Medicine
• microcephaly, seizures, and developmental delay

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2B2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.059386972 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PP5: Variant 19-49862369-A-G is Pathogenic according to our data. Variant chr19-49862369-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 206401.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKP	NM_007254.4	MANE Select	c.1029+2T>C		splice_donor intron	N/A	NP_009185.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKP	ENST00000322344.8	TSL:1 MANE Select	c.1029+2T>C		splice_donor intron	N/A	ENSP00000323511.2
	PNKP	ENST00000596014.5	TSL:1	c.1029+2T>C		splice_donor intron	N/A	ENSP00000472300.1
	PNKP	ENST00000593946.5	TSL:1	n.*956+2T>C		splice_donor intron	N/A	ENSP00000468896.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 157 AN: 144138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000602

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000236

Gnomad FIN AF: 0.00200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00106 AC: 158 AN: 149072 AF XY: 0.00109

Gnomad AFR exome AF: 0.000525

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00135

Gnomad NFE exome AF: 0.00212

Gnomad OTH exome AF: 0.000943

GnomAD4 exome AF: 0.00187 AC: 2120 AN: 1136252 Hom.: 0 Cov.: 34 AF XY: 0.00179 AC XY: 1016 AN XY: 567000

African (AFR) AF: 0.000156 AC: 4 AN: 25714

American (AMR) AF: 0.000385 AC: 13 AN: 33732

Ashkenazi Jewish (ASJ) AF: 0.000139 AC: 3 AN: 21546

East Asian (EAS) AF: 0.00 AC: 0 AN: 29442

South Asian (SAS) AF: 0.0000674 AC: 5 AN: 74186

European-Finnish (FIN) AF: 0.00130 AC: 54 AN: 41656

Middle Eastern (MID) AF: 0.000263 AC: 1 AN: 3802

European-Non Finnish (NFE) AF: 0.00229 AC: 1972 AN: 859300

Other (OTH) AF: 0.00145 AC: 68 AN: 46874

GnomAD4 genome AF: 0.00109 AC: 157 AN: 144240 Hom.: 0 Cov.: 32 AF XY: 0.00115 AC XY: 81 AN XY: 70546

African (AFR) AF: 0.000202 AC: 8 AN: 39558

American (AMR) AF: 0.00 AC: 0 AN: 14670

Ashkenazi Jewish (ASJ) AF: 0.000602 AC: 2 AN: 3324

East Asian (EAS) AF: 0.00 AC: 0 AN: 4634

South Asian (SAS) AF: 0.000237 AC: 1 AN: 4228

European-Finnish (FIN) AF: 0.00200 AC: 19 AN: 9504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00195 AC: 127 AN: 65136

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.000854

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00123 AC: 10

ExAC AF: 0.000272 AC: 27

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:25 Uncertain:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Microcephaly, seizures, and developmental delay Pathogenic:9

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was identified as compound heterozygous.

Oct 01, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 10, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

Oct 09, 2023

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 05, 2025

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

The c.1029+2T>C variant in PNKP has been reported in the compound heterozygous state in 4 individuals with microcephaly, seizures, and developmental delay and segregated with disease in 2 affected individuals from 2 families (Rudenskaya 2019 PMID: 31061747; Freitas 2021 PMID: 33654647; Neuser 2022 PMID: 34697416). It has also been identified in 0.2% (2099/924436) of European (non-Finnish) chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 206401). This variant occurs within the canonical splice site(+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the PNKP gene is an established disease mechanism in autosomal recessive microcephaly, seizures, and developmental delay. RNAseq showed exon 11 skipping, which is in-frame and is predicted to escape nonsense mediated decay (NMD) (Neuser 2021 PMID: 34697416; Wai 2020 PMID: 32123317). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive microcephaly, seizures, and developmental delay. ACMG/AMP Criteria applied: PM3_Strong, PVS1_Moderate, PP1.

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 05, 2022

DASA

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1029+2T>C variant is located in a canonical splice-site, and it is not predicted the protein reading frame alteration, however, occur in a critical region and the variant disrupts <10% of protein - PVS1_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 206401; PMID: 33654647, 31061747) - PS4_moderate. The variant is present at low allele frequencies population databases (rs199919568 – gnomAD 0.01089%; ABraOM 0.001281 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The c.1029+2T>C was detected in trans with a pathogenic variant (PMID: 31061747; 33654647) - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 31061747) - PP1. In summary, the currently available evidence indicates that the variant is likely pathogenic.

Oct 10, 2024

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with ataxia-oculomotor apraxia 4 (MIM#616267), and microcephaly, seizures, and developmental delay (MIM#613402). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). It has been suggested that this variant cases exon 11 skipping however, the relevant data was not shown (PMID: 32123317). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (190 heterozygotes, 0 homozygotes). (SP) 0311 - Multiple alternative nucleotide changes at the same canonical splice site are present in gnomAD (v4) (highest allele count: 2 heterozygotes, 0 homozygotes. (I) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity. A different variant in the same splice site (c.1029+1G>A) has been reported as pathogenic (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has been classified as pathogenic or likely pathogenic by multiple clinical laboratories in ClinVar and has been observed as compound heterozygous in six individuals from four families with ataxia-culomotor apraxia (PMIDs: 31061747, 33654647, 34697416). It has also been classified as a VUS or likely benign in ClinVar, but these submissions do not contain significant justification for the classification and are outweighed by the pathogenic and likely pathogenic submissions. (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

not provided Pathogenic:8 Uncertain:1

Jun 30, 2022

Revvity Omics, Revvity

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Dec 27, 2022

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 19, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM3, PS3_moderate, PVS1_strong

Nov 01, 2018

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 26, 2025

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RNA studies and functional RNA analyses demonstrate a damaging effect and indicate aberrant splicing in response to c.1029+2T>C resulting predominately in skipping of exon 11, affecting the phosphatase domain and the kinase domain (PMID: 37301908, 34697416, 22508754); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 31061747, 29655203, 29720203, 29261713, 22508754, 32123317, 34697416, Fontaine2022[Preprint], 33654647, 37301908, 38523675)

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PNKP: PM3:Strong, PP1:Strong, PVS1:Strong, PM2:Supporting

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ataxia - oculomotor apraxia type 4 Pathogenic:3

Oct 02, 2020

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

Apr 02, 2020

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2.

Mar 13, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: PNKP c.1029+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of PNKP function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. Two publications report experimental evidence that this variant affects mRNA splicing (Wai_2020, Oddsson_2023). The variant allele was found at a frequency of 0.0011 in 149072 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PNKP causing Ataxia - oculomotor apraxia type 4 (0.0011 vs 0.0011), allowing no conclusion about variant significance. c.1029+2T>C has been reported in the literature in individuals affected with PNKP-related disorders (Coll_2017, Lindy_2018, Freitas_2021). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 29261713, 33654647, 29655203, 37301908, 32123317). ClinVar contains an entry for this variant (Variation ID: 206401). Based on the evidence outlined above, the variant was classified as pathogenic.

Inborn genetic diseases Pathogenic:1

Jun 07, 2025

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1029+2T>C intronic variant results from a T to C substitution two nucleotides after exon 11 (coding exon 10) of the PNKP gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. A resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay. However, the region predicted to be impacted is critical for protein function (Ambry internal data). Based on data from gnomAD, the C allele has an overall frequency of 0.106% (190/178830) total alleles studied. The highest observed frequency was 0.208% (147/70858) of European (non-Finnish) alleles. This variant has been identified in conjunction with other PNKP variants in individuals with features consistent with PNKP-related neurological disorder and segregated with disease in at least one family; in at least one instance, the variants were identified in trans (Freitas, 2021; Rudenskaya, 2019; Neuser, 2022). This nucleotide position is highly conserved in available vertebrate species. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Oddsson, 2023; Wai, 2020; Neuser, 2022). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, this alteration is classified as pathogenic.

Abnormal cerebral morphology Pathogenic:1

Diagnostic Laboratory, Strasbourg University Hospital

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Charcot-Marie-Tooth disease type 2B2;C3150667:Microcephaly, seizures, and developmental delay;C4225397:Ataxia - oculomotor apraxia type 4 Pathogenic:1

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has been reported in the literature in the compound heterozygous state in at least 2 individuals with features of ataxia with oculomotor apraxia type 4 (AOA4) segregating with disease in 2 affected family members. This variant has also been identified in the heterozygous state in at least 3 individuals with epilepsy; however, at least 1 author has called into question the pathogenicity of this variant (Coll 2017 PMID:29261713, Stanek 2018 PMID:29720203, Lindy 2018 PMID:29655203, Rudenskaya 2019 PMID:310617747, Freitas 2021 PMID:33654647). This variant is present in the Genome Aggregation Database (Highest reported MAF 0.2% (127/65136) (https://gnomad.broadinstitute.org/variant/19-49862369-A-G?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Pathogenic or Likely Pathogenic; however, at least 1 laboratory has submitted a classification of Likely Benign for this variant (Variation ID:206401). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. RNA studies predict that this variant will impact the protein with altered splicing (Wai 2020 PMID:32123317). However, these studies may not accurately represent in vivo biological function. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Dumitrache 2017 PMID:27125728). However, this variant is expected to alter exon 11; this exon is in frame and represents less than 10% of the total protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.

Developmental and epileptic encephalopathy, 12 Pathogenic:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change affects a donor splice site in intron 11 of the PNKP gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs199919568, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individual(s) with clinical features of PNKP-related conditions (PMID: 31061747). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 206401). Studies have shown that disruption of this splice site results in skipping of exon 11 and/or intron 10 retention , and produces a non-functional protein and/or introduces a premature termination codon (PMID: 34697416, 37301908). For these reasons, this variant has been classified as Pathogenic.

Microcephaly, seizures, and developmental delay;C4225397:Ataxia - oculomotor apraxia type 4 Pathogenic:1

Feb 13, 2023

Genetics and Molecular Pathology, SA Pathology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Uncertain:1

Jun 24, 2020

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant classified as Uncertain Significance - Favor Pathogenic. The c.1029+2T>C variant in PNKP has been reported in the compound heterozygous state in one individual with Ataxia with Oculomotor Apraxia Type 4 and their affected sibling (Rudenskaya 2019 PMID: 31061747). It has also been identified in 3 individuals with epilepsy (Lindy 2018 PMID: 29655203, Stanek 2018 PMID: 29720203, Coll 2017 PMID: 29261713). It has also been reported by other clinical laboratories in ClinVar (Variation ID:206401) and has been identified in 0.2% (147/70858) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. However, exon 11, which is affected by this variant, is in frame and consists of only 93 base pairs and encodes less than 10% of the PNKP protein. The PNKP gene has been definitively been associated with autosomal recessive ataxia with oculomotor apraxia and with microcephaly, seizures, and developmental delay. However, there is limited evidence regarding its association with epilepsy. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain for autosomal recessive ataxia with oculomotor apraxia. ACMG/AMP Criteria applied: PVS1_Moderate, PM3, PP1_Supporting.

Microcephaly Uncertain:1

Sep 03, 2019

Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PNKP-related disorder Uncertain:1

Feb 12, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The PNKP c.1029+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in the compound heterozygous state in at least five individuals with severe progressive microcephaly, hypotonia, developmental delays, and ataxia-oculomotor apraxia type 4 (Neuser et al. 2021. PubMed ID: 34697416; Rudenskaya et al. 2019. PubMed ID: 31061747; Freitas et al. 2021. PubMed ID: 33654647). Functional studies confirm that this variant causes aberrant splicing by skipping exon 11, resulting in an in-frame deletion of amino acids 313-343 (Wai et al. 2020. PubMed ID: 32123317). This variant is reported in 0.21% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has conflicting interpretations regarding it pathogenicity in ClinVar, ranging from pathogenic to likely pathogenic to uncertain significance to likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/206401/). Loss of function is a known mechanism of disease for PNKP, and other splice altering changes have been reported as causative; however these other pathogenic variants are all found at lower frequency in gnomAD (Human Gene Mutation Database). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		3.2
GERP RS		5.1
Mutation Taster		=3/97	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
Splicevardb		3.0
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.93		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199919568; hg19: chr19-50365626;