Submissions for variant NM_005763.4(AASS):c.2762A>G (p.Gln921Arg)

gnomAD frequency: 0.00046  dbSNP: rs140285200

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238813	SCV000297193	uncertain significance	not specified	2015-10-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765927	SCV000897347	uncertain significance	Saccharopinuria; Hyperlysinemia	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001854920	SCV002255956	uncertain significance	not provided	2022-07-21	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 921 of the AASS protein (p.Gln921Arg). This variant is present in population databases (rs140285200, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with AASS-related conditions. ClinVar contains an entry for this variant (Variation ID: 252652). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV001854920	SCV004160980	uncertain significance	not provided	2022-06-01	criteria provided, single submitter	clinical testing	AASS: PM2, BP4