Submissions for variant NM_005787.6(ALG3):c.444+1G>A

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004783343	SCV005395042	likely pathogenic	ALG3-congenital disorder of glycosylation	2024-09-10	criteria provided, single submitter	clinical testing	Variant summary: ALG3 c.444+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of ALG3 function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 248950 control chromosomes. To our knowledge, no occurrence of c.444+1G>A in individuals affected with ALG3-congenital disorder of glycosylation and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.