Submissions for variant NM_000030.3(AGXT):c.166-14C>T

gnomAD frequency: 0.00486  dbSNP: rs180177176

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243175	SCV000301566	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000186233	SCV001302356	likely benign	Primary hyperoxaluria, type I	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000243175	SCV001338438	benign	not specified	2020-04-30	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.166-14C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0036 in 274786 control chromosomes, predominantly at a frequency of 0.0059 within the Non-Finnish European subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2 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. c.166-14C>T has been reported in the literature as a polymorphic variant (Williams_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001512368	SCV001719773	benign	not provided	2025-01-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001512368	SCV005261955	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000186233	SCV000239557	uncertain significance	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	research