13-51937503-GATGGCCACATCCGTGCCGGTGCCA-G
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP3PP5
The NM_000053.4(ATP7B):c.3852_3875del(p.Gly1285_Ile1292del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I1284I) has been classified as Likely benign.
Frequency
Consequence
NM_000053.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.3852_3875del | p.Gly1285_Ile1292del | inframe_deletion | 18/21 | ENST00000242839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7B | ENST00000242839.10 | c.3852_3875del | p.Gly1285_Ile1292del | inframe_deletion | 18/21 | 1 | NM_000053.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461718Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727146
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Wilson disease Pathogenic:1Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2023 | This variant, c.3852_3875del, results in the deletion of 8 amino acid(s) of the ATP7B protein (p.Gly1285_Ile1292del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Wilson's disease (PMID: 9222767). ClinVar contains an entry for this variant (Variation ID: 555278). This variant disrupts a region of the ATP7B protein in which other variant(s) (p.Thr1288Arg) have been determined to be pathogenic (PMID: 16416207, 17410460). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at