Submissions for variant NM_000262.3(NAGA):c.985C>T (p.Arg329Trp)

dbSNP: rs121434530

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767012	SCV005381135	likely pathogenic	Alpha-N-acetylgalactosaminidase deficiency	2024-08-14	criteria provided, single submitter	clinical testing	Variant summary: NAGA c.985C>T (p.Arg329Trp) results in a non-conservative amino acid change located in the Alpha galactosidase A, C-terminal beta-sandwich domain (IPR035373) 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 4e-06 in 251396 control chromosomes. c.985C>T has been reported in the literature in a homozygous individual affected with N-acetylgalactosaminidase alpha deficiency (example: Wang_1994). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Wang_1994). The following publication has been ascertained in the context of this evaluation (PMID: 8040340). ClinVar contains an entry for this variant (Variation ID: 18163). Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM	RCV000019793	SCV000040091	pathogenic	Alpha-N-acetylgalactosaminidase deficiency type 2	1994-08-01	no assertion criteria provided	literature only