Submissions for variant NM_005787.6(ALG3):c.611C>T (p.Ala204Val)

gnomAD frequency: 0.00001  dbSNP: rs1719034314

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	RCV003235585	SCV003933822	uncertain significance	not specified	2023-05-17	criteria provided, single submitter	clinical testing	Variant summary: ALG3 c.611C>T (p.Ala204Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 240440 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.611C>T has been reported in the literature in an individual affected with ALG3-congenital disorder of glycosylation (examples: Alsharhan_2021, and Farolfi_2021). These data do not allow any conclusion about variant significance. The following publications have been ascertained in the context of this evaluation (PMID: 33583022, 34090370). 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 uncertain significance.
University of Washington Center for Mendelian Genomics, University of Washington	RCV001543409	SCV001761968	pathogenic	ALG3-congenital disorder of glycosylation		no assertion criteria provided	research