Submissions for variant NM_000030.3(AGXT):c.866G>A (p.Arg289His)

gnomAD frequency: 0.00143  dbSNP: rs61729604

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000587981	SCV000232896	uncertain significance	not provided	2015-03-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265666	SCV000693981	uncertain significance	not specified	2022-05-26	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.866G>A (p.Arg289His) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00098 in 153122 control chromosomes, particularly at a frequency of 0.0036 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 phenotype (0.0024), suggesting that the variant may be a benign polymorphism. Nevertheless, c.866G>A has been reported in the literature in a homozygous individual affected with Primary Hyperoxaluria Type 1 (Murad_2021). It has also been reported as part of complex alleles in additional individuals affected with Primary Hyperoxaluria Type 1 (Williams_2009, Williams_2015). These reports do not provide unequivocal conclusions about association of the variant with Primary Hyperoxaluria Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign and three ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Counsyl	RCV000186341	SCV000800738	uncertain significance	Primary hyperoxaluria, type I	2017-12-19	criteria provided, single submitter	clinical testing
Invitae	RCV000587981	SCV001110251	likely benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000186341	SCV001297137	uncertain significance	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 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.
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000186341	SCV000239687	pathogenic	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	research