Submissions for variant NM_000485.3(APRT):c.200G>A (p.Arg67Gln)

dbSNP: rs762509151

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV001269438	SCV002021423	likely pathogenic	Adenine phosphoribosyltransferase deficiency	2021-04-23	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV001269438	SCV005438796	likely pathogenic	Adenine phosphoribosyltransferase deficiency	2023-07-22	criteria provided, single submitter	clinical testing	The missense c.200G>A p.Arg67Gln variant in the APRT gene which is located in a mutational hot spot has been reported previously in a homozygous and heterozygous state in individuals affected with adenine phosphoribosyltransferase APRT deficiency Lau et al., 2019; Taniguchi et al., 2004. This variant has been reported to the ClinVar database as Pathogenic/ Likely pathogenic. This variant is reported with the allele frequency 0.0004% in the gnomAD Exomes. The amino acid Arg at position 67 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence Polyphen - Damaging, SIFT - Damaging and MutationTaster - Disease causing predict a damaging effect on protein structure and function for this variant. The amino acid change p.Arg67Gln in APRT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Functional studies will be required to prove the pathogenicity. For these reasons, this variant has been classified as Likely Pathogenic.
APRT Deficiency Research Program of the Rare Kidney Stone Consortium, Landspitali, National University Hospital of Iceland	RCV001269438	SCV001449076	pathogenic	Adenine phosphoribosyltransferase deficiency	2020-09-01	no assertion criteria provided	literature only