rs1555284582

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000053.4(ATP7B):​c.3638G>T​(p.Gly1213Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

ATP7B
NM_000053.4 missense

Scores

16
2
1

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:1

Conservation

PhyloP100: 7.86
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.994
PP5
Variant 13-51939112-C-A is Pathogenic according to our data. Variant chr13-51939112-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 549999.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATP7BNM_000053.4 linkuse as main transcriptc.3638G>T p.Gly1213Val missense_variant 17/21 ENST00000242839.10 NP_000044.2 P35670-1B7ZLR4A0A024RDX3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP7BENST00000242839.10 linkuse as main transcriptc.3638G>T p.Gly1213Val missense_variant 17/211 NM_000053.4 ENSP00000242839.5 P35670-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:2Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Wilson disease Pathogenic:2Uncertain:1
Likely pathogenic, criteria provided, single submitterclinical testingCenter for Genomic Medicine, King Faisal Specialist Hospital and Research CenterSep 22, 2024- -
Likely pathogenic, criteria provided, single submitterclinical testingBaylor GeneticsMar 27, 2024- -
Uncertain significance, criteria provided, single submitterclinical testingCounsylApr 21, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.59
D
BayesDel_noAF
Pathogenic
0.60
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.98
D;D;.;.;.;.;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D
M_CAP
Pathogenic
0.87
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.8
H;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-8.0
D;D;D;D;D;.;D
REVEL
Pathogenic
0.97
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
0.91
MutPred
0.92
Loss of relative solvent accessibility (P = 0.0793);.;.;.;.;.;.;
MVP
0.98
MPC
0.41
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.99
gMVP
0.96

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.

Other links and lift over

dbSNP: rs1555284582; hg19: chr13-52513248; API