Submissions for variant NM_000053.4(ATP7B):c.1543+13C>T

gnomAD frequency: 0.00062  dbSNP: rs200171850

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000341242	SCV000384675	uncertain significance	Wilson disease	2018-01-12	criteria provided, single submitter	clinical testing	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.
CeGaT Center for Human Genetics Tuebingen	RCV000415979	SCV000493697	likely benign	not provided	2016-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000423547	SCV000522340	likely benign	not specified	2017-11-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000423547	SCV001442806	likely benign	not specified	2024-12-16	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.1543+13C>T alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing (TrAP). However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00084 in 248120 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ATP7B causing Wilson Disease (0.00084 vs 0.0054), allowing no conclusion about variant significance. c.1543+13C>T has been reported in the literature in individuals affected with Wilson Disease without strong evidence for causality (Coffey_2013). These report(s) 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. ClinVar contains an entry for this variant (Variation ID: 312390). Based on the evidence outlined above, the variant was classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000341242	SCV002383344	likely benign	Wilson disease	2025-01-30	criteria provided, single submitter	clinical testing