13-51950132-C-T

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM5PP5_Very_Strong

The NM_000053.4(ATP7B):c.2605G>A(p.Gly869Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,172 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G869V) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

ATP7B
NM_000053.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:25U:2

Conservation

PhyloP100: 7.82

Variant links:

Genes affected

ATP7B (HGNC:870): (ATPase copper transporting beta) This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein is a monomer, and functions as a copper-transporting ATPase which exports copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease which is characterized by copper accumulation. [provided by RefSeq, Dec 2019]

ATP7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PM1

In a topological_domain Cytoplasmic (size 133) in uniprot entity ATP7B_HUMAN there are 18 pathogenic changes around while only 3 benign (86%) in NM_000053.4

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

PP5

Variant 13-51950132-C-T is Pathogenic according to our data. Variant chr13-51950132-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 157939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-51950132-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4 link	c.2605G>A	p.Gly869Arg	missense_variant	Exon 11 of 21	ENST00000242839.10	NP_000044.2	P35670-1B7ZLR4A0A024RDX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10 link	c.2605G>A	p.Gly869Arg	missense_variant	Exon 11 of 21	1	NM_000053.4	ENSP00000242839.5		P35670-1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000693

AC:

173

AN:

249580

Hom.:

AF XY:

0.000598

AC XY:

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00132

AC:

1926

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

922

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152280

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00182

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000259

AC:

ESP6500EA

AF:

0.00157

AC:

ExAC

AF:

0.000678

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00130

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:25Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wilson disease

Pathogenic:18

Jun 30, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 19, 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: ATP7B c.2605G>A (p.Gly869Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00069 in 252586 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ATP7B causing Wilson Disease (0.00069 vs 0.0054), allowing no conclusion about variant significance. c.2605G>A has been reported in the literature in in numerous affected individuals without K-F rings in the literature, reported in late-onset patients with mild phenotype, and in some cases, in clinically asymptomatic individuals, although with abnormal biochemical findings (low plasma Cu and CP levels, elevated urinary Cu level). Therefore, this variant represents a mild mutation with a phenotypic outcome significantly dependent on a genetic background (Dong_2016, Ferenci_2007, Gu_2013, Mukherjee_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Pathogenic/likely pathogenic, n=7; VUS, n=1). Based on the evidence outlined above, the variant was classified as pathogenic. -

Nov 20, 2020

Molecular Genetics, Royal Melbourne Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change is predicted to replace glycine with arginine at codon 869 of the ATP7B protein (p.Gly869Arg). The glycine residue is highly conserved (100 vertebrates, UCSC), and is located in the proton ATPase domain. There is a large physicochemical difference between glycine and arginine. The variant is present in a large population cohort at a frequency of 0.07% (rs191312027, 206/280,980 alleles, 0 homozygotes in gnomAD v2.1). It has been identified compound heterozygous with other pathogenic alleles in multiple Wilson disease cases along with reduced serum ceruloplasmin and elevated urinary copper which establishes a biochemical diagnosis (PMID: 15952988, 23843956, 27398169, 30702195 - PM3_VeryStrong, PP4). Multiple lines of computational evidence predict a deleterious effect for the missense substitution (7/7 algorithms - PP3). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong, PP3, PP4. -

Jan 05, 2022

DASA

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2605G>A;p.(Gly869Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 157939; PMID: 23843956; 15952988; 27398169; 11093740; 30702195) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (E1-E2_ATPase domain) - PM1. The variant is present at low allele frequencies population databases (rs191312027– gnomAD 0.01032%; ABraOM 0.001708 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Gly869Arg) was detected in trans with a pathogenic variant (PMID: 23843956; 15952988; 27398169; 11093740; 30702195) - PM3_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. -

May 21, 2020

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_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0112 - Variants in this gene are known to have reduced penetrance (N) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine (exon 11). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (206 Heterozygotes, 0 Homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (2 Heterozygotes, 0 Homozygotes). (N) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif (PDB). (N) 0708 - Comparable variant has been reported as a VUS (LOVD). (N) 0801 - Strong previous evidence of pathogenicity in unrelated individuals (ClinVar, Li, X. et al. (2019), Mukherjee, S. et al. (2014), Shah, A. B. et al. (1997), Hua, R. et al. (2016), Bowling, K. M. et al. (2017)). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -

Oct 09, 2023

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 25, 2024

All of Us Research Program, National Institutes of Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This missense variant replaces glycine with arginine at codon 869 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Although functional studies have not been reported, this variant alters a conserved glycine residue in the A domain of the ATP7B protein that is involved in the ATP hydrolysis (a.a. 786 - 917), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). This variant has been reported in over twenty individuals affected with autosomal recessive Wilson disease, including up to ten individuals confirmed to be compound heterozygous with a known pathogenic variant in the same gene (PMID: 9311736, 15952988, 17433323, 23219664, 23518715, 23843956, 24094725, 27022412, 27398169, 30702195, 31980526, 33159804, 33258288; Castellano et al., 2023 EASL Congress). This variant has been identified in 206/280980 chromosomes (161/128724 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. This variant is reported to show reduced penetrance and is associated with a mild phenotype in compound heterozygous individuals with Wilson disease (PMID: 32248359, 33159804; Castellano et al., 2023 EASL Congress). -

Feb 10, 2015

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 869 of the ATP7B protein (p.Gly869Arg). This variant is present in population databases (rs191312027, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Wilson disease (PMID: 11093740, 15952988, 23843956, 27398169, 30702195). ClinVar contains an entry for this variant (Variation ID: 157939). 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 ATP7B protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. -

Mar 30, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 13, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The ATP7B c.2605G>A; p.Gly869Arg variant (rs191312027) is reported in the medical literature in several individuals with a clinical diagnosis of Wilson disease, many of whom carried an additional pathogenic variant (Dong 2016, Gu 2013, Hua 2016, Huang2022, Li 2019, Loudianos 2013, Margarit 2005, Mukherjee 2014). This variant is found in the European population with an overall allele frequency of 0.13% (161/128724 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.876). Considering available information, this variant is considered to be likely pathogenic. References: Dong Y et al. Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis. Theranostics. 2016 Mar 3;6(5):638-49. PMID: 27022412. Gu S et al. Novel ATPase Cu(2+) transporting beta polypeptide mutations in Chinese families with Wilson's disease. PLoS One. 2013 Jul 2;8(7):e66526. PMID: 23843956. Hua R et al. Mutational analysis of ATP7B in Chinese Wilson disease patients. Am J Transl Res. 2016 Jun 15;8(6):2851-61. PMID: 27398169. Huang C et al. Genetic studies discover novel coding and non-coding mutations in patients with Wilson's disease in China. J Clin Lab Anal. 2022 Jun;36(6):e24459. PMID: 35470480. Li X et al. Complex ATP7B mutation patterns in Wilson disease and evaluation of a yeast model for functional analysis of variants. Hum Mutat. 2019 May;40(5):552-565. PMID: 30702195. Loudianos G et al. Wilson's disease in two consecutive generations: the detection of three mutated alleles in the ATP7B gene in two Sardinian families. Dig Liver Dis. 2013 Apr;45(4):342-5. PMID: 23219664. Margarit E et al. Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet. 2005 Jul;68(1):61-8. PMID: 15952988. Mukherjee S et al. Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation. Parkinsonism Relat Disord. 2014 Jan;20(1):75-81. PMID: 24094725. -

Feb 01, 2024

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Sep 02, 2021

Revvity Omics, Revvity

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 20, 2013

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 20, 2021

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Gly869Arg variant in ATP7B has been reported 6 individuals with Wilson disease, all of whom were compound heterozygous (Garcia-Villarreal 2000 PMID: 11093740, Margarit 2005 PMID: 15952988, Gu 2013 PMID: 23843956, Hua 2016 PMID: 27398169, Li 2019 PMID: 30702195). This variant has also been reported in ClinVar (Variation ID#3848). This variant has also been identified in 0.125% (161/128724) of European chromosomes by Genome Aggregation Database (gnomAD, Http://gnomad.broadinstitute.org). This frequency is consistent with the known carrier frequency of Wilson disease. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly869Arg variant is likely pathogenic for Wilson disease in an autosomal recessive manner. ACMG/AMP Criteria applied: PM3_VStrong; PP3, PP4. -

Aug 21, 2023

Color Diagnostics, LLC DBA Color Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 15, 2021

Genetics and Molecular Pathology, SA Pathology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Pathogenic:5Uncertain:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATP7B: PM3:Very Strong, PM5, PM2:Supporting -

May 23, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PP3, PP4_moderate, PM2, PS4_moderate -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 14, 2022

AiLife Diagnostics, AiLife Diagnostics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 12, 2024

GeneDx

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Described as a mild variant associated with reduced penetrance as it has been observed in association with late-onset, a mild phenotype, and in asymptomatic adult twins from a single family (PMID: 11093740, 32248359, 22692182, 23219664); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11093740, 18371106, 17433323, 17949296, 27022412, 23518715, 24720933, 24094725, 27398169, 30702195, 30097039, 32248359, 22692182, 15952988, 9311736, 23843956, 34426522, 33159754, 33258288, 31980526, 35637795, 35470480, 35844287, 30275481, 35314707, 36253962, 34620762, 33159804, 35220961, 34405919, 30254379, 36437915, 37445923, 36910591, 23219664, 34381985, 37147621, 37937776, 31708252, 39198578, 39322449, Kerr[article]2024) -

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

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 08, 2015

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Pathogenic:1

Jul 02, 2024

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2605G>A (p.G869R) alteration is located in coding exon 11 of the ATP7B gene. This alteration results from a G to A substitution at nucleotide position 2605, causing the glycine (G) at amino acid position 869 to be replaced by an arginine (R). Based on data from gnomAD, the A allele has an overall frequency of 0.073% (206/280980) total alleles studied. The highest observed frequency was 0.125% (161/128724) of European (non-Finnish) alleles. This variant was detected in an individual in conjunction with p.L708P and a mild presentation with normal liver biopsy, near normal ceruloplasmin levels, elevated liver and urinary copper levels, and was diagnosed with Wilson disease at age 26 (Garcia Villarreal, 2000). This variant was in trans with p.D765G in an individual with neurologic symptoms, hepatosplenomegaly, jaundice, Kayser-Fleischer rings, and elevated urinary copper levels (Gu, 2013). In addition, several other individuals with this and a second variant presented with a hepatic phenotype (Margarit, 2005; Hua, 2016), a Parkinsonian-like phenotype (Margarit, 2005), and a mild Wilson disease phenotype (Schushan, 2012). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. -

ATP7B-related disorder

Pathogenic:1

Sep 03, 2024

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ATP7B c.2605G>A variant is predicted to result in the amino acid substitution p.Gly869Arg. This variant was reported in the compound heterozygous state in many individuals with varied features consistent with Wilson disease (Shah et al. 1997. PubMed ID: 9311736; Margarit et al. 2005. PubMed ID: 15952988; Hua et al. 2016. PubMed ID: 27398169; Gu et al. 2013. PubMed ID: 23843956; Huang et al. 2022. PubMed ID: 35470480). However, this variant is also reported in 0.16% of alleles in individuals of European (non-Finnish) descent including 3 homozygotes in gnomAD v4.0.0. This higher than expected allele frequency is consistent with this variant being a mild or possibly low penetrance variant (García-Villarreal et al. 2000. PubMed ID: 11093740; Wallace et al. 2020. PubMed ID: 32248359). For example, this variant was reported with the p.Met645Arg variant in an individual with late onset (50 years old), mild Wilson disease (Schushan et al. 2012. PubMed ID: 22692182). In summary, this variant is interpreted as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.96

D;D;.;.;.;.;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.70

MetaRNN

Uncertain

0.66

D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.7

H;.;.;.;.;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.4

D;D;D;D;D;.;D

REVEL

Pathogenic

0.88

Sift

Uncertain

0.0010

D;D;D;D;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D

Vest4

0.77

MutPred

0.94

Gain of solvent accessibility (P = 0.0306);.;.;.;.;.;Gain of solvent accessibility (P = 0.0306);

MVP

0.98

MPC

0.40

ClinPred

0.32

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over