Submissions for variant NM_000030.3(AGXT):c.454T>A (p.Phe152Ile)

gnomAD frequency: 0.00016  dbSNP: rs121908524

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000005999	SCV000486336	pathogenic	Primary hyperoxaluria, type I	2016-05-11	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727639	SCV000854923	pathogenic	not provided	2018-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779687	SCV000916431	pathogenic	Primary hyperoxaluria	2018-07-02	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.454T>A (p.Phe152Ile) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 248758 control chromosomes (gnomAD). The variant, c.454T>A, has been reported in the literature in multiple individuals affected with Primary Hyperoxaluria Type 1 (van der Hoeven_2012, Monico_2007). These data indicate that the variant is very likely to be associated with disease. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000727639	SCV001232267	pathogenic	not provided	2024-01-26	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 152 of the AGXT protein (p.Phe152Ile). This variant is present in population databases (rs121908524, gnomAD 0.02%). This missense change has been observed in individual(s) with hyperoxaluria (PMID: 8101040, 11708860, 25363903). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 5645). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGXT protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects AGXT function (PMID: 10960483). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000005999	SCV002813829	pathogenic	Primary hyperoxaluria, type I	2021-12-14	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000005999	SCV004194638	pathogenic	Primary hyperoxaluria, type I	2023-09-18	criteria provided, single submitter	clinical testing
OMIM	RCV000005999	SCV000026181	pathogenic	Primary hyperoxaluria, type I	2013-01-25	no assertion criteria provided	literature only
GeneReviews	RCV000005999	SCV000172452	not provided	Primary hyperoxaluria, type I		no assertion provided	literature only
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000005999	SCV000223918	pathogenic	Primary hyperoxaluria, type I	2014-05-13	no assertion criteria provided	clinical testing
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000005999	SCV000239641	pathogenic	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	in vitro
Natera, Inc.	RCV000005999	SCV001456047	pathogenic	Primary hyperoxaluria, type I	2020-09-16	no assertion criteria provided	clinical testing