13-51934740-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_000053.4(ATP7B):c.*16G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,612,330 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000053.4 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.*16G>A | 3_prime_UTR_variant | Exon 21 of 21 | ENST00000242839.10 | NP_000044.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000985 AC: 150AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00111 AC: 276AN: 248388Hom.: 1 AF XY: 0.00113 AC XY: 152AN XY: 134858
GnomAD4 exome AF: 0.00114 AC: 1662AN: 1459958Hom.: 2 Cov.: 30 AF XY: 0.00111 AC XY: 803AN XY: 726322
GnomAD4 genome AF: 0.000984 AC: 150AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.00106 AC XY: 79AN XY: 74508
ClinVar
Submissions by phenotype
Wilson disease Uncertain:1Benign:1
- -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Uncertain:1
Variant summary: ATP7B c.*16G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0011 in 1612330 control chromosomes, predominantly at a frequency of 0.0013 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ATP7B causing Wilson Disease (0.0011 vs 0.0054), allowing no strong conclusion about variant significance. c.*16G>A has been reported in the literature as a VUS in at least one individual affected with Wilson Disease as well as in unaffected controls (example, Stalke_2018, Coffey_2013). These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23518715, 28776642). ClinVar contains an entry for this variant (Variation ID: 35734). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. -
not provided Benign:1
This variant is associated with the following publications: (PMID: 28776642) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at