rs886038218
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000053.4(ATP7B):c.1912G>T(p.Ala638Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A638T) has been classified as Likely benign.
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.1912G>T | p.Ala638Ser | missense_variant | 6/21 | ENST00000242839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7B | ENST00000242839.10 | c.1912G>T | p.Ala638Ser | missense_variant | 6/21 | 1 | NM_000053.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151962Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
Wilson disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 31, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 638 of the ATP7B protein (p.Ala638Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7B protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at