Submissions for variant NM_000030.3(AGXT):c.32C>T (p.Pro11Leu)

dbSNP: rs34116584

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000173049	SCV000224129	benign	not specified	2014-09-24	criteria provided, single submitter	clinical testing
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000005995	SCV000239543	likely benign	Primary hyperoxaluria, type I	2023-12-23	criteria provided, single submitter	clinical testing	c.32C>T, although a common polymorphic variant with approximately 64% activity in vitro (PMID:10960483), it can influence the pathogenicity of some AGXT variants, for example see c.836T>C
PreventionGenetics, part of Exact Sciences	RCV000173049	SCV000301569	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000005995	SCV000429355	likely benign	Primary hyperoxaluria, type I	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000173049	SCV001338182	benign	not specified	2023-02-24	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.32C>T (p.Pro11Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.15 in 246868 control chromosomes, predominantly at a frequency of 0.2 within the Non-Finnish European subpopulation in the gnomAD database, including 2253 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 101 fold of the estimated maximal expected allele frequency for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 phenotype (0.0024), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. However, the variant, c.32C>T, has also been reported in the literature in multiple individuals affected with Primary Hyperoxaluria Type 1, together with two pathogenic variants (VanWoerden_2004, Lorenzo_2006, Kanoun_2013, Ahmed_2022). Clinical and functional data show that this variant leads to a synergistic effect with some common pathogenic variants (e.g. Gly170Arg and p.Ile244Thr), and the presence of this variant in the same chromosome (in cis) is required for their loss of function effect (Lumb_2000, Santana_2003, Monico_2007). Four ClinVar submitters (evaluation after 2014) cite this variant as benign (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001513552	SCV001721185	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000005995	SCV002802776	likely benign	Primary hyperoxaluria, type I	2021-09-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001513552	SCV005261953	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000005995	SCV000026177	benign	Primary hyperoxaluria, type I	2013-01-25	no assertion criteria provided	literature only
GeneReviews	RCV000005995	SCV000172447	not provided	Primary hyperoxaluria, type I		no assertion provided	literature only
Natera, Inc.	RCV000005995	SCV001462981	benign	Primary hyperoxaluria, type I	2020-01-10	no assertion criteria provided	clinical testing