Submissions for variant NM_000091.5(COL4A3):c.-10C>T

gnomAD frequency: 0.00039  dbSNP: rs781380101

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001143023	SCV001303520	uncertain significance	Alport syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003490085	SCV004241233	likely benign	not specified	2023-12-18	criteria provided, single submitter	clinical testing	Variant summary: COL4A3 c.-10C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00028 in 1530590 control chromosomes in the gnomAD database, including 4 homozygotes. c.-10C>T has been reported in the literature in individuals affected with Alport Syndrome, however the authors indicate it is likely a co-occurring polymorphism, suggesting a benign role (e.g., Vega_2003). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 14582039). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Immunogenetics and Transplant Biology Service, University Hospital "Città della Salute e della Scienza di Torino"	RCV003991040	SCV004037597	likely benign	Autosomal dominant Alport syndrome	2023-07-03	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003938498	SCV004759610	likely benign	COL4A3-related disorder	2020-03-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).