rs755584106
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000053.4(ATP7B):c.4114C>T(p.Gln1372Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,068 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q1372Q) has been classified as Likely benign.
Frequency
Consequence
NM_000053.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.4114C>T | p.Gln1372Ter | stop_gained | 20/21 | ENST00000242839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7B | ENST00000242839.10 | c.4114C>T | p.Gln1372Ter | stop_gained | 20/21 | 1 | NM_000053.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246332Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 133988
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461068Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726756
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Wilson disease Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 29, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 22, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ATP7B protein in which other variant(s) (p.Arg1459Glyfs*2) have been determined to be pathogenic (PMID: 26799313). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 371170). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 27398169, 30884209). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs755584106, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Gln1372*) in the ATP7B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 94 amino acid(s) of the ATP7B protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at