chr16-13947991-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PP3PP5BP4BS1_Supporting

The NM_005236.3(ERCC4):c.2395C>T(p.Arg799Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000629 in 1,614,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00077 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

ERCC4
NM_005236.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:20U:5O:2

Conservation

PhyloP100: 5.39

Publications

49 publications found

Variant links:

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

ERCC4 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group F
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, ClinGen
Fanconi anemia complementation group Q
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
XFE progeroid syndrome
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum-Cockayne syndrome complex
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERCC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

PP5

Variant 16-13947991-C-T is Pathogenic according to our data. Variant chr16-13947991-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 16580.

BP4

Computational evidence support a benign effect (MetaRNN=0.09623465). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000768 (117/152286) while in subpopulation NFE AF = 0.000764 (52/68024). AF 95% confidence interval is 0.000599. There are 1 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ERCC4	NM_005236.3 link	c.2395C>T	p.Arg799Trp	missense_variant	Exon 11 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4 link	c.2533C>T	p.Arg845Trp	missense_variant	Exon 12 of 12		XP_011520726.1
ERCC4	XM_047433774.1 link	c.1606C>T	p.Arg536Trp	missense_variant	Exon 8 of 8		XP_047289730.1
ERCC4	XM_011522427.2 link	c.1045C>T	p.Arg349Trp	missense_variant	Exon 6 of 6		XP_011520729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.2395C>T	p.Arg799Trp	missense_variant	Exon 11 of 11	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000481

AC:

121

AN:

251312

AF XY:

0.000442

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000889

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000614

AC:

898

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

467

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000748

AC:

832

AN:

1112008

Other (OTH)

AF:

0.000248

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152286

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41574

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000737

Hom.:

Bravo

AF:

0.000948

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000511

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:20Uncertain:5Other:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group F

Pathogenic:8

Jun 18, 2024

Institute of Human Genetics Munich, TUM University Hospital

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 01, 1998

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Feb 22, 2022

MGZ Medical Genetics Center

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 21, 2021

Undiagnosed Diseases Network, NIH

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Wangler Lab, Baylor College of Medicine

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense ERCC4 variant at c.2395C>T (p.R799W) was seen on exome through the Texome project (R01HG011795). This variant has been described in individuals with ERCC4-related conditions (PMID: 8797827, 9579555, 20221251, 27528516). It has been observed in gnomAD with a frequency of 0.040% in the heterozygous state and has not been observed in the homozygous state (PM2). Functional studies suggest this variant is functionally defective (PMID: 9579555, 20221251) (PS3).This variant is predicted to be deleterious (CADD: 31.000) (PP3). The evolutionary conservation of this residue is high. We classify this variant as pathogenic.

Dec 19, 2018

Illumina Laboratory Services, Illumina

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Across a selection of the available literature, the ERCC4 c.2395C>T (p.Arg799Trp) variant has been identified in 11 probands with xeroderma pigmentosum including five in a homozygous state, four in a heterozygous state and two in a compound heterozygous state (Sijbers et al. 1996; Sijbers et al. 1998; Gregg et al. 2011). The p.Arg799Trp variant is reported at a frequency of 0.001 in the European American population of the Exome Sequencing Project. Functional rescue studies showed that the variant could only partially rescue the nuclear excision repair defect and that the variant protein mislocalized to the cytoplasm (Sijbers et al. 1998; Ahmad et al. 2010). Based on the collective evidence, the p.Arg799Trp variant is classified as pathogenic for xeroderma pigmentosum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

Oct 28, 2021

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The ERCC4 c.2395C>T (p.Arg799Trp) missense change has a maximum subpopulation frequency of 0.081% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/16-14041848-C-T). Six of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), and in vitro functional assays in LCLs (Epstein–Barr virus transformed lymphoblastoid cell lines) and fibroblasts have shown that this variant causes reduced protein expression of nuclear ERCC4 which is attributed to protein mislocalization and can result in decreased cell survival and DNA replication after ultraviolet light exposure (PS3; PMID: 20221251, 29105242, 9579555). This variant has been reported in over ten individuals affected with xeroderma pigmentosum (PS4, PM3; PMID: 8797827, 9579555, 23623389, 21228398, 28431612, 29892709). In addition, it has been reported in three individuals with autosomal recessive cerebellar ataxia with mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn (PMID: 29403087), one individual with sporadic ataxia (PMID: 31692161), two individuals with head and neck squamous cell carcinoma (PMID: 28678401), one individual with sporadic pancreatic adenocarcinoma (PMID: 28767289), one individual with Cockayne syndrome (PMID: 29105242), and one individual with colorectal cancer (PMID: 31871297). This variant is also known as p.Arg788Trp in the literature. In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied: PS3, PS4, PM3, PP3.

Baylor Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Pathogenic:3Uncertain:1

Oct 23, 2020

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ERCC4: PM3:Very Strong, PM2:Supporting, PS3:Supporting

May 25, 2022

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Published functional studies demonstrate R799W decreased activity compared to wild-type (Ahmad et al., 2010).; This variant is associated with the following publications: (PMID: 26074087, 20221251, 24728327, 9579555, 22941649, 23623386, 21612988, 23623389, 18628313, 28678401, 27356891, 29376097, 28376890, 8797827, 28767289, 28431612, 29403087, 27528516, 21228398, 29105242, 34426522, 30665703, 31692161, 31980526, 31871297, 29892709)

Nov 03, 2021

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

Xeroderma pigmentosum

Pathogenic:2

Jul 07, 2025

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

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: ERCC4 c.2395C>T (p.Arg799Trp) results in a non-conservative amino acid change located in the ERCC4 domain (IPR006166) of the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 0.00048 in 251312 control chromosomes, predominantly at a frequency of 0.00089 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 4.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in ERCC4 causing Xeroderma Pigmentosum phenotype (0.00019). c.2395C>T has been observed in multiple homozygous and compound heterozygous individuals affected with mild features of Xeroderma Pigmentosum associated with later onset neurodegeneration/ataxia/chorea/variant forms of Cockayne syndrome/XP-F complementation group (Sijbers_1998, Ahmad_2010, Marelli_2016, Carre_2017, Ngo_2020, Kashiyama_2013, Shanbag_2018, Doi_2018, Mori_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Sijbers_1998, Ahmad_2010). The most pronounced variant effect results in approximately 20% of normal Nucleotide Excision Repair (NER) activity. The following publications have been ascertained in the context of this evaluation (PMID: 20221251, 28431612, 29403087, 23623389, 27528516, 29105242, 31692161, 29892709, 9579555). ClinVar contains an entry for this variant (Variation ID: 16580). Based on the evidence outlined above, the variant was classified as likely pathogenic.

Nov 02, 2021

Sema4, Sema4

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:curation

Fanconi anemia complementation group Q

Pathogenic:1Uncertain:1

Mar 04, 2021

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

May 16, 2024

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The ERCC4 c.2395C>T (p.Arg799Trp) missense change has a maximum subpopulation frequency of 0.081% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, however in vitro functional assays in LCLs (Epstein–Barr virus transformed lymphoblastoid cell lines) and fibroblasts have shown that this variant causes reduced protein expression of nuclear ERCC4 which is attributed to protein mislocalization and can result in decreased cell survival and DNA replication after ultraviolet light exposure (PMID: 20221251, 29105242, 9579555). This variant has been reported in over ten individuals affected with xeroderma pigmentosum (PMID: 8797827, 9579555, 23623389, 21228398, 28431612, 29892709). In addition, it has been reported in three individuals with autosomal recessive cerebellar ataxia with mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn (PMID: 29403087), one individual with sporadic ataxia (PMID: 31692161), two individuals with head and neck squamous cell carcinoma (PMID: 28678401), one individual with sporadic pancreatic adenocarcinoma (PMID: 28767289), one individual with Cockayne syndrome (PMID: 29105242), and one individual with colorectal cancer (PMID: 31871297). This variant is also known as p.Arg788Trp in the literature. In summary, this variant meets criteria to be classified as pathogenic.

Xeroderma pigmentosum, group F;C1970416:XFE progeroid syndrome;C3808988:Fanconi anemia complementation group Q

Pathogenic:1Uncertain:1

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

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ERCC4 NM_005236 exon 11 p.Arg799Trp (c.2395C>T): This variant has been reported in the literature in at least 5 individuals with features or a diagnosis of Xeroderma Pigmentosum-F as compound heterozygous or homozygous (Sijbers 1996 PMID: 8797827, Sijbers 1998 PMID:9579555, Kashiyama 2013 PMID:23623389, Marelli 2016 PMID:27528516, Carre 2017 PMID:28431612). This variant is present in 103/126562 Caucasian individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs121913049). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population and/or variable expressivity. This variant is present in ClinVar (Variation ID:16580). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, functional studies have shown a deleterious effect of this variant (Sijbers 1998 PMID:9579555, de Laat 1998 PMID:9722633). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain

Mar 23, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q

Pathogenic:1Other:1

GenomeConnect - Invitae Patient Insights Network

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Pathogenic and reported on 12-16-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 799 of the ERCC4 protein (p.Arg799Trp). This variant is present in population databases (rs121913049, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of ERCC4-related conditions (PMID: 8797827, 20221251, 23623389, 26074087, 27356891, 27528516, 28431612, 28678401, 28767289, 29105242, 29403087, 29892709). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.2377C>T, p.Arg788Trp. ClinVar contains an entry for this variant (Variation ID: 16580). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ERCC4 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ERCC4 function (PMID: 9579555, 20221251). For these reasons, this variant has been classified as Pathogenic.

not specified

Uncertain:1Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Present in 1/908 alleles in the other population and in 55/66734 European alleles of ExAC. Reported by Sijbers_1996 in a compound heterozygous individual with XP group F.

Carcinoma of pancreas

Pathogenic:1

Mar 04, 2021

CZECANCA consortium

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:case-control

XFE progeroid syndrome

Pathogenic:1

Apr 04, 2019

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

ERCC4-related disorder

Pathogenic:1

Feb 22, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

The ERCC4 c.2395C>T variant is predicted to result in the amino acid substitution p.Arg799Trp. This variant has been reported in the compound heterozygous and homozygous state in patients affected with xeroderma pigmentosum (F) (reported as R788W in Sijbers et al. 1996. PubMed ID: 8797827 and Sijbers et al. 1998. PubMed ID: 9579555; HGMD# CM960516 in Table S9 in Bell et al. 2011. PubMed ID: 21228398; Doi et al. 2018. PubMed ID: 29403087; Shanbhag et al. 2018. PubMed ID: 29892709; Marelli et al. 2016. PubMed ID: 27528516; Kashiyama et al. 2013. PubMed ID: 23623389). This variant has also been identified in individuals with pancreatic adenocarcinoma (Shindo et al. 2017. PubMed ID: 28767289), head and neck squamous cell carcinoma (Chandrasekharappa et al. 2017. PubMed ID: 28678401), and colorectal cancer (Goldstein et al. 2020. PubMed ID: 31871297), but was also found in healthy control individuals (Table 2, Dobbins et al. 2016. PubMed ID: 27356891; Bodian et al. 2014. PubMed ID: 24728327). In Dobbins et al. 2016 paper the authors conclude that they did not observe a significant difference in the frequency of pathogenic variants between cases and controls in their cohort. This variant is reported in 0.081% of alleles in individuals of European (non-Finnish) descent in gnomAD. Based on the available evidence, this variant is interpreted as likely pathogenic for autosomal recessive ERCC4-related disease.

Hutchinson-Gilford syndrome

Pathogenic:1

University of Washington Center for Mendelian Genomics, University of Washington

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

Breast carcinoma

Uncertain:1

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.0019

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.55

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.7

PhyloP100

5.4

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.91

ClinPred

0.31

GERP RS

6.2

Varity_R

0.93

gMVP

0.83

Mutation Taster

=17/83

disease causing (ClinVar)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over