chr13-51949742-T-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_StrongBP6BS2_Supporting
The NM_000053.4(ATP7B):āc.2785A>Gā(p.Ile929Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,614,126 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. I929M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.2785A>G | p.Ile929Val | missense_variant | 12/21 | ENST00000242839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7B | ENST00000242839.10 | c.2785A>G | p.Ile929Val | missense_variant | 12/21 | 1 | NM_000053.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000911 AC: 227AN: 249300Hom.: 3 AF XY: 0.000835 AC XY: 113AN XY: 135286
GnomAD4 exome AF: 0.000194 AC: 283AN: 1461806Hom.: 2 Cov.: 36 AF XY: 0.000205 AC XY: 149AN XY: 727210
GnomAD4 genome AF: 0.000440 AC: 67AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47AN XY: 74484
ClinVar
Submissions by phenotype
Wilson disease Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 29, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 15, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 23, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
ATP7B-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 06, 2016 | Variant summary: The ATP7B c.2785A>G (p.Ile929Val) variant involves the alteration of a non-conserved nucleotide. Ile929 is located in the transmembrane domain, is highly conserved across species, and 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). However, yeast functional analyses showed no significant effect of this I929V. Additionally, this variant was found in 131/121316 control chromosomes (1 homozygote), predominantly observed in the East Asian subpopulation at a frequency of 0.0131243 (113/8610). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple sources, including a clinical diagnostic laboratory, a database, and publications, classified this variant as benign. Taken together, this variant is classified as Benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at