chr13-51937537-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000053.4(ATP7B):c.3842G>T(p.Gly1281Val) 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 Uncertain significance (★★).
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.3842G>T | p.Gly1281Val | missense_variant | Exon 18 of 21 | ENST00000242839.10 | NP_000044.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Wilson disease Uncertain:3
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This sequence change replaces glycine with valine at codon 1281 of the ATP7B protein (p.Gly1281Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Wilson disease (Invitae). 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 (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Gly1281 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been observed in individuals with ATP7B-related conditions (PMID: 17272994; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
PP3, PM2_moderate -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at