Submissions for variant NM_000091.5(COL4A3):c.346C>A (p.Pro116Thr)

gnomAD frequency: 0.00485  dbSNP: rs115324397

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000248076	SCV000302074	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000710817	SCV000730618	benign	not provided	2018-05-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24854265, 14871398, 30245029, 29924831)
Athena Diagnostics	RCV000710817	SCV000841122	benign	not provided	2019-07-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000248076	SCV000919244	likely benign	not specified	2018-01-08	criteria provided, single submitter	clinical testing	Variant summary: The COL4A3 c.346C>A (p.Pro116Thr) variant involves the alteration of a conserved nucleotide located in the Collagen triple helix repeat domain of the protein (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1348/277088 control chromosomes (7 homozygotes), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.008757 (1109/126648). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic COL4A3 variant (0.0020412), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in multiple affected individuals without stong evidence for causality. In addition, one other clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000710817	SCV001099364	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001138282	SCV001298323	benign	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV001171336	SCV001328283	likely benign	Chronic kidney disease	2020-05-28	criteria provided, single submitter	research	PP3, BP6, BS1
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000248076	SCV001652983	benign	not specified	2021-02-17	criteria provided, single submitter	clinical testing	The p.Pro116Thr variant in COL4A3 is classified as benign because it has been identified in 0.9% (1119/128642) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported as benign and likely benign in ClinVar (Variation ID 254994). ACMG/AMP criteria applied: BA1, BP4.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294100	SCV002587267	benign	Focal segmental glomerulosclerosis	2022-08-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710817	SCV004151540	benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	COL4A3: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000710817	SCV005259006	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001138282	SCV002076377	benign	Alport syndrome	2019-11-14	no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000248076	SCV003839363	benign	not specified	2022-09-13	no assertion criteria provided	clinical testing