rs192044702

Variant names:

• chr3-81648854-A-G
• rs192044702
• NM_000158.4:c.691+2T>C

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1 PP5_Very_Strong

The NM_000158.4(GBE1):​c.691+2T>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,502,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: GBE1 NM_000158.4 splice_donor, intron
• Scores: Splicing: ADA: 0.9964
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:33
• Conservation: PhyloP100: 8.95
• Publications: 16 publications found

Genes affected

GBE1 (HGNC:4180): (1,4-alpha-glucan branching enzyme 1) The protein encoded by this gene is a glycogen branching enzyme that catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, in reducing the osmotic pressure within cells. Highest level of this enzyme are found in liver and muscle. Mutations in this gene are associated with glycogen storage disease IV (also known as Andersen's disease). [provided by RefSeq, Jul 2008]

GBE1 Gene-Disease associations (from GenCC):

• glycogen storage disease due to glycogen branching enzyme deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics, G2P, ClinGen
• adult polyglucosan body disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 16 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PP5: Variant 3-81648854-A-G is Pathogenic according to our data. Variant chr3-81648854-A-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 208584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.691+2T>C		splice_donor_variant, intron_variant	Intron 5 of 15	ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.819+2T>C		splice_donor_variant, intron_variant	Intron 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.691+2T>C		splice_donor_variant, intron_variant	Intron 5 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.568+2T>C		splice_donor_variant, intron_variant	Intron 5 of 15	2		ENSP00000419638.1
GBE1	ENST00000498468.1	n.219+2T>C		splice_donor_variant, intron_variant	Intron 2 of 3	3
GBE1	ENST00000486920.1	n.*113T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000756 AC: 115 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000895 AC: 173 AN: 193326 AF XY: 0.000797

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000999

Gnomad ASJ exome AF: 0.000259

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00152

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00103 AC: 1396 AN: 1349858 Hom.: 0 Cov.: 22 AF XY: 0.000989 AC XY: 661 AN XY: 668278

African (AFR) AF: 0.0000713 AC: 2 AN: 28064

American (AMR) AF: 0.0000668 AC: 2 AN: 29940

Ashkenazi Jewish (ASJ) AF: 0.000300 AC: 7 AN: 23344

East Asian (EAS) AF: 0.00 AC: 0 AN: 36232

South Asian (SAS) AF: 0.00 AC: 0 AN: 68302

European-Finnish (FIN) AF: 0.000831 AC: 42 AN: 50554

Middle Eastern (MID) AF: 0.000197 AC: 1 AN: 5076

European-Non Finnish (NFE) AF: 0.00125 AC: 1314 AN: 1052456

Other (OTH) AF: 0.000501 AC: 28 AN: 55890

GnomAD4 genome AF: 0.000756 AC: 115 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74402

African (AFR) AF: 0.000240 AC: 10 AN: 41584

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 67924

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000775 Hom.: 0

Bravo AF: 0.000654

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00160 AC: 13

ExAC AF: 0.000936 AC: 113

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:33

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:14

May 09, 2024

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Identified in patients with features of GBE1-related glycogen storage disease or GBE1-related polyglucosan body disease referred for genetic testing at GeneDx or in published literature (PMID: 23218673, 19813197, 28507268); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 33060286, 34626176, 33879512, 23352160, 23218673, 25489661, 28507268, 31980526, 31862442, 30569318, 29379554, 31589614, 33726816, 32528171, 33332610, 31127727, 32668698, 34426522, 33820833, 35627109, 37273706, 37301908, 26166723, 19813197) -

Mar 05, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 02, 2016

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Pathogenic

Review Status: no assertion criteria provided

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 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GBE1: PM3:Very Strong, PVS1, PM2, PP1:Moderate -

Nov 21, 2022

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 23, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PP1, PP3, PS3, PS4_moderate, PVS1 -

Glycogen storage disease, type IV Pathogenic:10

Jan 27, 2022

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

The c.691+2T>C variant in GBE1 has been reported in at least 10 individuals with GBE1-related disorders (PMID: 19813197, 23218673, 25489661, 26166723, 26886200, 28507268, 29379554, 30569318, Akman 2015, Thomsen 2016) and has been identified in 0.1% (160/110918) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs192044702). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. Of the many affected individuals, 1 was a compound heterozygote that carried a reported likely pathogenic variant in trans, and 2 were compound heterozygotes that carried a reported pathogenic variant with unknown phase, which increases the likelihood that the c.691+2T>C variant is pathogenic (Variation ID#: 2777; PMID: 25489661, 28507268, Akman 2015). This variant has also been reported in ClinVar (Variation ID#: 208584) and has been interpreted as pathogenic by multiple submitters. The phenotype of individuals homozygous or compound heterozygous for this variant is highly specific for GBE1-related disorders based on strict biochemical investigations consistent with disease (PMID: 19813197, 23218673). This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. Loss of function of the GBE1 gene is an established disease mechanism in autosomal recessive GBE1-related disorders. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive GBE1-related disorders. ACMG/AMP Criteria applied: PVS1, PM3_strong, PP4 (Richards 2015). -

Aug 22, 2022

MGZ Medical Genetics Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 03, 2017

Counsyl

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Dec 06, 2018

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant affects the canonical splice donor site of intron 5 of 15, and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has been previously reported as a compound heterozygous change in patients with GBE1 glycogen storage disease (PMID: 23218673, 19813197). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.082% (183/223430; max AF: 0.0013 in European populations) and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.691+2T>C variant is classified as Pathogenic. -

Feb 03, 2020

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. -

Sep 16, 2020

Natera, Inc.

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 27, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 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_v1.3.4, 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 glycogen storage disease IV (GSD-IV) (MIM#232500) and adult form polyglucosan body disease (MIM#263570). (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). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (194 heterozygotes, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic in multiple patients with either GSD-IV or adult form polyglucosan body disease (LOVD, ClinVar, PMID: 29379554). (SP) 1207 - Parental origin of the variant is unresolved. The proband and both parents are heterozygous for this variant (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -

Aug 27, 2021

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: GBE1 c.691+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. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00089 in 193326 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in GBE1 causing Glycogen Storage Disease, Type IV (0.00089 vs 0.0013), allowing no conclusion about variant significance. c.691+2T>C has been reported in the literature in several compound heterozygous individuals affected with Glycogen Storage Disease, Type IV (e.g. Fernandez_2010, Ravenscroft_2013, Bendroth-Asmussen_2016, Schene_2018, Szymanska_2018). These data indicate that the variant is likely to be associated with disease. Several publications also reported severely reduced enzyme activities in patient derived cells (e.g. Fernandez_2010, Ravenscroft_2013, Schene_2018, Szymanska_2018). 13 submitters have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Aug 09, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

GBE1-related disorder Pathogenic:2

Oct 13, 2017

Illumina Laboratory Services, Illumina

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The GBE1 c.691+2T>C splice donor variant has been reported in a total of seven individuals, including five with glycogen storage disease type IV (GSD IV) and two with adult polyglucosan body disease (APBD) (Fernandez et al. 2010; Ravenscroft et al. 2013; Bendroth-Asmussen et al. 2016; Kuhn et al. 2016; Franco-Palacios et al. 2016; Lopez Chiriboga 2017). All five individuals with GSD IV and one individual with APBD were compound heterozygous for the variant. In addition, one individual with APBD was heterozygous for the c.691+2T>C variant and homozygous for another intronic variant in the GBE1 gene (Franco-Palacios et al. 2016). The c.691+2T>C variant was also identified in a heterozygous state in two unaffected individuals (Ravenscroft et al. 2013; Dainese et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00196 in the European (non-Finnish) population of the Exome Aggregation Consortium. Two studies noted significantly reduced GBE enzyme activity in individual fibroblasts (Fernandez et al. 2010; Ravenscroft et al. 2013). Based on the evidence and due to the potential impact of splice donor variants, the p.691+2T>C variant is classified as pathogenic for GBE1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -

Nov 01, 2023

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The GBE1 c.691+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 two presumably unrelated families, one of which included siblings initially diagnosed with lethal multiple pterygium syndrome (Fernandez et al. 2010. PubMed ID: 19813197; Ravenscroft et al. 2013. PubMed ID: 23218673). More recently, this variant was identified in the compound heterozygous state with a second pathogenic GBE1 variant in tissue from a fetus lost in a first trimester miscarriage. Histopathological findings in the fetal tissue were consistent with glycogen storage disease type IV (GSD IV) (Bendroth-Asmussen et al. 2016. PubMed ID: 26166723). At PreventionGenetics, we have observed this variant in combination with a second pathogenic variant in at least two unrelated affected patients. This variant is reported in 0.14% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-81698005-A-G). Variants that disrupt the consensus splice donor site in GBE1 are expected to be pathogenic. This variant is interpreted as pathogenic. -

Glycogen storage disease, type IV;C1849722:Adult polyglucosan body disease Pathogenic:1

May 09, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Pathogenic:1

Feb 20, 2024

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.691+2T>C intronic alteration results from a T to C substitution two nucleotides after coding exon 5 of the GBE1 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay; however, +2T>C alterations are capable of generating wild-type transcripts in some genomic contexts and should be interpreted with caution (Lin, 2019). Based on data from gnomAD, the C allele has an overall frequency of 0.086% (194/224704) total alleles studied. The highest observed frequency was 0.144% (160/110918) of European (non-Finnish) alleles. This variant has been identified in the homozygous state and likely in trans with another GBE1 variant in multiple individuals and fetuses with features consistent with neuromuscular subtypes of GBE1-related glycogen storage disease, including biochemical or histological confirmation (Fernandez, 2010; Ravenscroft, 2013; Bendroth-Asmussen, 2016; Schene, 2019; Lef&egrave;vre, 2023). This nucleotide position is highly conserved in available vertebrate species. 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. -

Dementia Pathogenic:1

Feb 04, 2020

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glycogen storage disease Pathogenic:1

Jun 16, 2020

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.691+2T>C variant in GBE1 has been reported in at least 3 compound heterozygous individuals with glycogen storage disease IV and segregated with disease in at least 2 affected relatives from 1 family (Fernandez 2010 PMID:19813197, Ravenscroft 2013 PMID:23218673, Schene 2018 PMID:30569318). It has also been reported in ClinVar (Variation ID 208584) and has been identified in 0.14% (160/110918) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. 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 GBE1 gene is an established disease mechanism in autosomal recessive glycogen storage disease IV. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive glycogen storage disease IV. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PP1_Moderate. -

Adult polyglucosan body disease Pathogenic:1

Sep 28, 2023

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Criteria applied: PVS1,PM3_VSTR,PM2_SUP -

Arthrogryposis syndrome Pathogenic:1

Apr 17, 2019

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

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic Pathogenic:1

Jan 23, 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 5 of the GBE1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GBE1 are known to be pathogenic (PMID: 15452297, 20058079). This variant is present in population databases (rs192044702, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individual(s) with glycogen storage disease type IV (PMID: 19813197, 23218673, 26166723, 30569318). 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: 208584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		8.9
GERP RS		6.1
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.69
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.94		Position offset: 2

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

Other links and lift over

dbSNP: rs192044702; hg19: chr3-81698005;