13-51937570-T-C

Variant names:

• chr13-51937570-T-C
• rs121907990
• NM_000053.4:c.3809A>G

Variant summary

Our verdict is Pathogenic. The variant received 17 ACMG points: 17P and 0B. PM1 PM5 PP2 PP3_Strong PP5_Very_Strong

The NM_000053.4(ATP7B):​c.3809A>G​(p.Asn1270Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,614,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1270I) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: ATP7B NM_000053.4 missense
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:23 U:1
• Conservation: PhyloP100: 7.97

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]

ACMG classification

Our verdict: Pathogenic. The variant received 17 ACMG points.

• PM1: In a hotspot region, there are 8 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 8 uncertain in NM_000053.4
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr13-51937570-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1685251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 198 curated pathogenic missense variants (we use a threshold of 10). The gene has 32 curated benign missense variants. Gene score misZ: -0.88091 (below the threshold of 3.09). Trascript score misZ: 0.82063 (below the threshold of 3.09). GenCC associations: The gene is linked to Wilson disease.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958
• PP5: Variant 13-51937570-T-C is Pathogenic according to our data. Variant chr13-51937570-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 3859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-51937570-T-C is described in Lovd as [Pathogenic]. Variant chr13-51937570-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.3809A>G	p.Asn1270Ser	missense_variant	Exon 18 of 21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.3809A>G	p.Asn1270Ser	missense_variant	Exon 18 of 21	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000216 AC: 54 AN: 249580 AF XY: 0.000244

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000120 AC: 176 AN: 1461886 Hom.: 1 Cov.: 35 AF XY: 0.000131 AC XY: 95 AN XY: 727246

Gnomad4 AFR exome AF: 0.000119 AC: 4 AN: 33480

Gnomad4 AMR exome AF: 0.000671 AC: 30 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.000202 AC: 8 AN: 39700

Gnomad4 SAS exome AF: 0.000174 AC: 15 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53412

Gnomad4 NFE exome AF: 0.0000980 AC: 109 AN: 1112012

Gnomad4 Remaining exome AF: 0.000149 AC: 9 AN: 60396

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.000551 AC XY: 41 AN XY: 74378

Gnomad4 AFR AF: 0.0000723 AC: 0.0000723345 AN: 0.0000723345

Gnomad4 AMR AF: 0.00308 AC: 0.00307511 AN: 0.00307511

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206868 AN: 0.000206868

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000588 AC: 0.0000587924 AN: 0.0000587924

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000110 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000483 AC: 2

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.000149 AC: 18

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:23 Uncertain:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wilson disease Pathogenic:17 Uncertain:1

Mar 14, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: flagged submission

Collection Method: clinical testing

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1270 of the ATP7B protein (p.Asn1270Ser). This variant is present in population databases (rs121907990, gnomAD 0.08%). This missense change has been observed in individuals with Wilson disease (PMID: 20485189, 26269689, 27398169). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3859). 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%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 9654149, 22240481). For these reasons, this variant has been classified as Pathogenic. -

Jun 14, 2023

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A homozygous missense variant in exon 18 of the ATP7B gene that results in the amino acid substitution of Serine for Asparagine at codon 1270 (p.Asn1270Ser) was detected. The p.Asn1270Ser variant has not been reported in the 1000 genomes databases and has a minor allele frequency of 0.04%, 0.02% and 0.03% in the gnomAD (v3.1), gnomdAD (v2) and topmed databases respectively. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 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 asparagine with serine at codon 1270 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. This variant alters a residue in the phosphorylation domain of the ATP7B protein (a.a. 1004 - 1031 and a.a. 1197 - 1306), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). Functional studies in Chinese hamster ovary cells have shown the mutant protein to exhibit significantly reduced copper uptake and transport, and increased phosphorylation relative to wild type (PMID: 22240481). In a separate study, this variant was unable to rescue function in a knockout ccc2 yeast model (PMID: 9654149). This variant has been reported in many individuals affected with Wilson disease (PMID: 7626145, 9311736, 9452121, 10790207, 12544487, 17587212, 18483695, 19419418, 16696937, 23235335, 23518715, 25982861, 26269689, 27398169). In a number of these individuals, this variant was confirmed to be in the homozygous state or in the compound heterozygous state with a second pathogenic variant (PMID: 10790207, 12544487, 18483695, 23518715). This variant has been identified in 55/280972 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -

Dec 22, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The ATP7B c.3809A>G; p.Asn1270Ser variant (rs121907990) is reported in the literature in numerous individuals affected with Wilson disease (Abuduxikuer 2015, Barada 2010, Daneshjoo 2018, Guggilla 2015, Hua 2016, Tanzi 1993, Todorov 2005). This variant has been reported to cosegregate with disease in families, both in the homozygous state (Barada 2010, Tanzi 1993) and in trans to another pathogenic variant (Daneshjoo 2018). The asparagine at codon 1270 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.896). Biochemical analyses indicate this variant has severely reduced copper transport activity (Huster 2012), and it fails to rescue growth defects of mutant yeast to the extent of wildtype protein (Iida 1998). Additionally, other variants at this codon (p.Asn1270Asp, p.Asn1270Ile) have been reported in Wilson disease patients (Nemeth 2016, Tuan Pham 2017). The p.Asn1270Ser variant is reported in ClinVar (Variation ID: 3859), and is found in the general population with an overall allele frequency of 0.020% (55/280972 alleles, including a single homozygote) in the Genome Aggregation Database. Based on available information, the p.Asn1270Ser variant is considered to be pathogenic. References: Abuduxikuer K et al. Wilson disease with hepatic presentation in an eight-month-old boy. World J Gastroenterol. 2015 Aug 7;21(29):8981-4. PMID: 26269689. Barada K et al. Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: association with liver disease. J Clin Gastroenterol. 2010 Jul;44(6):432-9. PMID: 20485189. Daneshjoo O and Garshasbi M. Novel compound heterozygote mutations in the ATP7B gene in an Iranian family with Wilson disease: a case report. J Med Case Rep. 2018 Mar 15;12(1):68. PMID: 29540233. Guggilla SR et al. Spectrum of mutations in the ATP binding domain of ATP7B gene of Wilson Disease in a regional Indian cohort. Gene. 2015 Sep 10;569(1):83-7. PMID: 25982861. 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. Huster D et al. Diverse functional properties of Wilson disease ATP7B variants. Gastroenterology. 2012 Apr;142(4):947-956.e5. PMID: 22240481. Iida M et al. Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae. FEBS Lett. 1998 May 29;428(3):281-5. PMID: 9654149. Nemeth D et al. Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson's Disease. Gastroenterol Res Pract. 2016;2016:4548039. PMID: 26819605. Tanzi RE et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993 Dec;5(4):344-50. PMID: 8298641. Todorov T et al. Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. Clin Genet. 2005 Nov;68(5):474-6. PMID: 16207219. Tuan Pham LA et al. Genetic analysis of 55 northern Vietnamese patients with Wilson disease: seven novel mutations in ATP7B. J Genet. 2017 Dec;96(6):933-939. PMID: 29321352. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 25, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 11, 2020

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Asn1270Ser variant in ATP7B has been identified in >50 probands across multiple ethnic groups with Wilson disease, including at least 4 homozygotes and >15 compound heterozygotes, and has segregated in at least 4 affected siblings (Abuduxikuer 2015, Barada2010, Bost 2012, Chen 2019, Coffey 2013, Daneshjoo 2018, Deguti 2004, Dong 2016, Guggilla 2015, Hua 2016, Kuppala 2009, Li 2013, Okada 2000, Shah 1997, Wan 2010, Yoo 2002, Zali 2011). This variant has also been identified in 0.08% (30/35376) of Latino chromosomes, including 1 homozygote by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with a recessive allele frequency given an estimated prevalence of 1/30000 for Wilson disease. In vitro functional studies suggest that the variant may impact protein function (Huster 2012, Lida 1998), and computational prediction tools and conservation analysis suggest that this variant may impact the protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Wilson disease. ACMG/AMP criteria applied: PM3_VeryStrong, PP1_Strong, PP3, PP4, PS3_Supporting. -

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Mar 06, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This missense variant replaces asparagine with serine at codon 1270 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. This variant alters a residue in the phosphorylation domain of the ATP7B protein (a.a. 1004 - 1031 and a.a. 1197 - 1306), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). Functional studies in Chinese hamster ovary cells have shown the mutant protein to exhibit significantly reduced copper uptake and transport, and increased phosphorylation relative to wild type (PMID: 22240481). In a separate study, this variant was unable to rescue function in a knockout ccc2 yeast model (PMID: 9654149). This variant has been reported in many individuals affected with Wilson disease (PMID: 7626145, 9311736, 9452121, 10790207, 12544487, 17587212, 18483695, 19419418, 16696937, 23235335, 23518715, 25982861, 26269689, 27398169). In a number of these individuals, this variant was confirmed to be in the homozygous state or in the compound heterozygous state with a second pathogenic variant (PMID: 10790207, 12544487, 18483695, 23518715). This variant has been identified in 55/280972 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -

Aug 09, 2023

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 02, 2018

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.3809A>G (p.Asn1270Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 120980 control chromosomes. This frequency is not higher than expected for a pathogenic variant in ATP7B causing Wilson Disease (0.00015 vs 0.0054), allowing no conclusion about variant significance. c.3809A>G has been reported in the literature in numerous individuals affected with Wilson Disease as both a homozygous and compound heterozygous allele. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence on the variant and showed that copper uptake and transport are both defective (Huster_2012). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Mar 06, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 03, 2020

Myriad Genetics, Inc.

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NM_000053.3(ATP7B):c.3809A>G(N1270S) is classified as pathogenic in the context of Wilson Disease. Sources cited for classification include the following: PMID 23518715, 12544487, 22240481, 10790207, 9452121, 9829905, 19419418, 9311736, 7626145 and 9654149. Classification of NM_000053.3(ATP7B):c.3809A>G(N1270S) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. -

Feb 01, 2024

Neuberg Centre For Genomic Medicine, NCGM

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The above variant has been previously reported in homozygous and compound heterozygous states in multiple individuals affected with Wilson disease (Nayagam JS, et al., 2023). This variant has been observed to segregate with disease in related individuals. Functional studies indicate that this variant demonstrates impaired chloride transport and hyperphosphorylation and affects copper transport, supporting a damaging effect (Iida et al., 1998; Huster et al., 2012). -

not provided Pathogenic:4

Apr 21, 2022

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Published functional studies indicate that this variant leads to hyperphosphorylation and affects copper transport, supporting a damaging effect (Iida et al., 1998; Huster et al., 2012); 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: 24253677, 20485189, 22240481, 9654149, 29540233, 8298641, 32154060, 30655162, 23518715, 30275481, 25637381, 22692182, 25982861, 26269689, 27398169, 10194254, 9829905, 19419418, 7626145, 9452121, 12544487, 10790207, 9311736, 30558096, 31708252, 34324271, 31589614, 34426522, 34240825, 34470610, Huong2022[article], 35222532, 33879678, Rosa2022[article], 34002136, 35395623) -

May 17, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PP3, PP4, PP5, PM2_moderate, PS3, PS4_moderate -

Nov 11, 2016

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATP7B: PM2, PM3, PM5, PP1, PP4, PS3:Supporting, PS4:Supporting -

Inborn genetic diseases Pathogenic:1

Aug 03, 2017

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.N1270S pathogenic mutation (also known as c.3809A>G), located in coding exon 18 of the ATP7B gene, results from an A to G substitution at nucleotide position 3809. The asparagine at codon 1270 is replaced by serine, an amino acid with highly similar properties. This mutation has been identified in multiple individuals with Wilson disease, including several homozygous individuals (Yoo HW. Genet. Med. 2002;4:43S-48S; Deguti MM et al. Hum. Mutat., 2004 Apr;23:398; Barada K et al. J. Clin. Gastroenterol., 2010 Jul;44:432-9). When expressed in Sf9 cells, this mutation demonstrated impaired chloride transport and hyperphosphorylation (Huster D et al. Gastroenterology, 2012 Apr;142:947-956.e5). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

ATP7B-related disorder Pathogenic:1

Nov 03, 2023

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ATP7B c.3809A>G variant is predicted to result in the amino acid substitution p.Asn1270Ser. This variant has been repeatedly documented as causative for Wilson disease (Tanzi et al. 1993. PubMed ID: 8298641; Yoo et al. 2002. PubMed ID: 12544487; Zhang et al. 2013. PubMed ID: 23235335). Functional studies suggest that this variant alters normal protein function (Table S1, Schushan et al. 2012. PubMed ID: 22692182). In summary, we interpret this variant as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.97	D;D;.;.;.;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.2	H;.;.;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D;.;D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;D;D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D;D
Vest4		0.96
MVP		1.0
MPC		0.34
ClinPred		0.62	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.91
Mutation Taster		=10/90	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs121907990; hg19: chr13-52511706;