rs145843073

Variant names:

• chr15-89327198-T-C
• rs145843073
• NM_002693.3:c.1402A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM1 BP4_Strong

The NM_002693.3(POLG):​c.1402A>G​(p.Asn468Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,614,230 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N468S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (1 hom.)
• Consequence: POLG NM_002693.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:9 U:17 B:1
• Conservation: PhyloP100: 2.97
• Publications: 25 publications found

Genes affected

POLG (HGNC:9179): (DNA polymerase gamma, catalytic subunit) Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

POLG Gene-Disease associations (from GenCC):

• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial DNA depletion syndrome 4a

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P
• autosomal dominant progressive external ophthalmoplegia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive progressive external ophthalmoplegia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial neurogastrointestinal encephalomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• recessive mitochondrial ataxia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spinocerebellar ataxia with epilepsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 13 uncertain in NM_002693.3
• BP4: Computational evidence support a benign effect (MetaRNN=0.024409533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLG	NM_002693.3	c.1402A>G	p.Asn468Asp	missense_variant	Exon 7 of 23	ENST00000268124.11	NP_002684.1
POLG	NM_001126131.2	c.1402A>G	p.Asn468Asp	missense_variant	Exon 7 of 23		NP_001119603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLG	ENST00000268124.11	c.1402A>G	p.Asn468Asp	missense_variant	Exon 7 of 23	1	NM_002693.3	ENSP00000268124.5

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000473 AC: 119 AN: 251488 AF XY: 0.000456

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.000589

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000829 AC: 1212 AN: 1461886 Hom.: 1 Cov.: 34 AF XY: 0.000792 AC XY: 576 AN XY: 727244

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000614 AC: 53 AN: 86258

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53414

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000920 AC: 1023 AN: 1112010

Other (OTH) AF: 0.000695 AC: 42 AN: 60396

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000738 AC XY: 55 AN XY: 74500

African (AFR) AF: 0.000264 AC: 11 AN: 41590

American (AMR) AF: 0.00163 AC: 25 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000663 Hom.: 0

Bravo AF: 0.000695

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000445 AC: 54

EpiCase AF: 0.000927

EpiControl AF: 0.000771

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:9 Uncertain:17 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Pathogenic:3 Uncertain:6

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 09, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 20, 2022

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM3 -

Apr 17, 2018

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2024

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features associated with this gene. In multiple individuals, this variant has been seen where an alternate explanation for disease was also identified, suggesting this variant is unlikely to cause disease. Polyphen and MutationTaster yielded discordant predictions regarding whether this amino acid change is damaging to the protein. -

Apr 07, 2025

GeneDx

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Identified in three members of a family with CPEO, peripheral neuropathy, parkinsonism, and multiple mtDNA deletions in muscle who were also heterozygous for another POLG variant on the other allele; the authors could not conclusively determine whether p.(N468D) was related to the phenotype as siblings carrying p.(N468D) were unaffected (PMID: 15351195, 15181170); Identified as homozygous in an infant with Aicardi-Goutires syndrome who was also homozygous for a pathogenic variant in TREX1 (PMID: 33683010); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24122062, 19578034, 24508722, 28284481, 31669236, 32391929, 32347949, 29029963, 29712893, 16401742, 24259288, 21880868, 34426522, 22647225, 23811324, 19752458, 15181170, 32234506, 33513296, 23921535, 35114397, 36291626, 33683010, 35641312, 15351195, 24331360, 25193669, 37138020, 30255931, 31658717, 29997391, 30373890, 23426270) -

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 02, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POLG: PM2:Supporting, BP4 -

Progressive sclerosing poliodystrophy Pathogenic:2 Benign:1

Mar 27, 2024

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2018

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NM_002693.2:c.1402A>G (NP_002684.1:p.Asn468Asp) [GRCH38: NC_000015.10:g.89327198T>C] variant in POLG gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:15351195 ; 16401742 . This variant meets the following evidence codes reported in the ACMG-guideline. PS4:Prevalence of variant in affecteds statistically increased over controls. PS1:This variation causes same amino-acid change as an established pathogenic variant. PS3:Well established functional studies show a deleterious effect on POLG. Based on the evidence criteria codes applied, the variant is suggested to be Pathogenic. -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Pathogenic:1 Uncertain:1

Nov 04, 2020

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Mar 24, 2022

MGZ Medical Genetics Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Progressive sclerosing poliodystrophy;C1834846:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1;C1843851:Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis;C3150914:Mitochondrial DNA depletion syndrome 4b;C4225153:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1;C4551995:Mitochondrial DNA depletion syndrome 1 Uncertain:2

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 25, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

POLG-related disorder Pathogenic:1

May 30, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The POLG c.1402A>G variant is predicted to result in the amino acid substitution p.Asn468Asp. This variant has been reported in individuals with autosomal recessive POLG-related mitochondrial disease (Palin et al. 2013. PubMed ID: 23811324; Luoma et al. 2004. PubMed ID: 15351195; Woodbridge et al. 2013. PubMed ID: 22647225; González-Vioque et al. 2006. PubMed ID: 16401742; Buzkova et al. 2018. PubMed ID: 30373890). Some POLG variants have also been implicated in autosomal dominant progressive external ophthalmoplegia (PEO), and several PEO patients have been reported to carry this variant in the heterozygous state (Schulte et al. 2009. PubMed ID: 19752458). However, in a second family, heterozygous carriers of the c.1402A>G (p.Asn468Asp) variant were reportedly asymptomatic (Luoma et al. 2004. PubMed ID: 15351195). In ClinVar, this variant has conflicting interpretations of uncertain, likely pathogenic, and pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/206596/). This variant is reported in 0.072% of alleles in individuals of European (Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic for autosomal recessive disease. -

Progressive sclerosing poliodystrophy;C1834846:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1;C1843851:Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis;C3150914:Mitochondrial DNA depletion syndrome 4b;C4225153:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 Pathogenic:1

-

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POLG NM_002693.2 exon 16 p.Gly848Ser (c.2542G>A): This variant has been reported in the literature in the compound heterozygous or homozygous state in several individuals with autosomal recessive progressive external opthalmoplegia as well as a wide variety of additional POLG-related phenotypes (Lamantea 2002 PMID:12210792, Weiss 2010 PMID:20513108, Milone 2011 PMID:21670405, Tang 2011 PMID:21880868, Scalais 2012 PMID:22342071, Uusimaa 2013 PMID:23448099, Simon 2014 PMID:2014 PMID:24272679). Literature suggests that this variant is one of the most common pathgenic variants in the POLG gene (Hakonen, 2007 PMID:17426723, Tang 2011 PMID:21880868). This variant is present in 0.03% (40/129136) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-89865023-C-T). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:13502). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, functional studies indicate that this variant leads to decreased enzyme activity and reduced DNA binding affinity (Kasivishwanathan 2009 PMID:19478085). However, these studies may not accurately represent in vivo biological function. In summary, this variant is classified as pathogenic based on the data above. -

Progressive sclerosing poliodystrophy;C3150914:Mitochondrial DNA depletion syndrome 4b Pathogenic:1

-

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

POLG-Related Spectrum Disorders Uncertain:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 Uncertain:1

Sep 01, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The POLG c.1402A>G; p.Asn468Asp variant is reported in the literature in individuals affected with autosomal recessive progressive external ophthalmoplegia (Luoma 2004, Palin 2013, Woodbridge 2013). The affected individuals identified in these reports were compound heterozygous for the p.Asn468Asp variant while heterozygous carriers in the same family were unaffected. The variant has also been shown to co-segregate with disease in families with autosomal recessive progressive external ophthalmoplegia (Wanrooij 2004). This variant is reported with conflicting interpretations in ClinVar (Variation ID: 206596). Another variant in this region, p.Ala467Thr, is considered the most common pathogenic POLG variant (Variation ID: 13496). However, due to limited functional evidence, the clinical significance of the p.Asn468Asp variant is uncertain. -

Inborn genetic diseases Uncertain:1

Jul 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1402A>G (p.N468D) alteration is located in exon 7 (coding exon 6) of the POLG gene. This alteration results from a A to G substitution at nucleotide position 1402, causing the asparagine (N) at amino acid position 468 to be replaced by an aspartic acid (D). The altered amino acid is not conserved throughout evolution:_x000D_ _x000D_ The p.N468 amino acid is not conserved in available vertebrate species. The alteration is predicted benign by in silico models:_x000D_ _x000D_ The p.N468D alteration is predicted to be benign by Polyphen and tolerated by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Lennox-Gastaut syndrome Uncertain:1

Dec 05, 2016

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary spastic paraplegia Uncertain:1

Apr 01, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Uncertain:1

Aug 07, 2024

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: POLG c.1402A>G (p.Asn468Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00047 in 251488 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in POLG causing POLG-Related Spectrum Disorders, allowing no conclusion about variant significance. c.1402A>G has been reported in the literature in individuals affected with variety of POLG-related phenotypes. The variant has been reported in three affected family members (and no unaffected family members) with progressive external ophthalmoplegia and parkinsonism as well as a patient with early onset Parkinson's disease, all with a second variant of unknown significance (Luoma_2004, Ylonen_2017). Additionally, the variant was reported along with a pathogenic variant in cases of progressive external ophthalmoplegia and tetraparesis and mitochondrial neurogastrointestinal encephalopathy (Gonzalez-Vioque_2006, Woodbridge_2013). The variant has also been reported in the homozygous state in a patient with congenital ataxia who had no features suggestive of a POLG-related phenotype, therefore ITPR1 variants were considered resposible for congenital ataxia in this patient (Valence_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31658717, 16401742, 15351195, 15181170, 22647225, 29029963, 29997391). ClinVar contains an entry for this variant (Variation ID: 206596). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -

Mitochondrial disease Uncertain:1

Jun 11, 2020

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Variants in the centre of motif B in the polymerase domain (highly conserved active site), result in dominant disease (PMID: 28480171). (N) 0200 - Variant is predicted to result in a missense amino acid change from an asparagine to an aspartate (exon 7). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (138 heterozygotes, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (6 heterozygotes, 0 homozygotes). (N) 0504 - Same amino acid change has been observed in mammals. (B) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0808 - Previous reports of pathogenicity are conflicting. It has been reported as compound heterozygous with another variant in patients with progressive external ophthalmoplegia. However, it has been classified as both pathogenic and VUS in ClinVar (PMID: 22647225, 16401742). (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -

Progressive sclerosing poliodystrophy;C1843851:Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis;C3150914:Mitochondrial DNA depletion syndrome 4b Uncertain:1

Jan 28, 2022

New York Genome Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.42
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.95	L;L
PhyloP100		3.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.24
Sift	Benign	0.72	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;B
Vest4		0.44
MVP		0.84
MPC		0.18
ClinPred		0.0045	T
GERP RS		2.7
PromoterAI		0.0078	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.15
gMVP		0.22
Mutation Taster		=28/72	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs145843073; hg19: chr15-89870429;