13-51937537-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_000053.4(ATP7B):c.3842G>A(p.Gly1281Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.3842G>A | p.Gly1281Asp | missense_variant | Exon 18 of 21 | ENST00000242839.10 | NP_000044.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249564Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135402
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461872Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74392
ClinVar
Submissions by phenotype
Wilson disease Pathogenic:2Uncertain:2
This missense variant replaces glycine with aspartic acid at codon 1281 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 for this variant, it alters a conserved glycine residue in the phosphorylation domain of the ATP7B protein, which plays an important role in ATP7B protein function (PMID: 35245129; ClinVar). This variant has been reported in at least seven individuals affected with Wilson Disease (PMID: 17272994, 22484412, 22677543, 34400371, 32808274, 35782615; DOI: 10.2174/1876517300901010001; ClinVar SCV001500599.11), including one individual who was confirmed to carry another pathogenic variant in trans (PMID: 17272994) and two individuals who carried another pathogenic variant in unknown phase (PMID: 32808274; ClinVar SCV001500599.11). This variant has been identified in 2/249564 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -
- -
- -
- -
not provided Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at