Submissions for variant NM_000487.6(ARSA):c.1108-1G>C

dbSNP: rs2146718041

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	RCV002222915	SCV002500256	likely pathogenic	Metachromatic leukodystrophy	2022-03-09	criteria provided, single submitter	clinical testing	Variant summary: ARSA c.1108-1G>C alters a conserved nucleotide 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. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' splice acceptor site. Four predict the variant strengthens an alternate exonic 3' splice acceptor site that is predicted to result in a frameshifted protein. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 249706 control chromosomes. To our knowledge, no occurrence of c.1108-1G>C in individuals affected with Metachromatic Leukodystrophy and no experimental evidence demonstrating its impact on protein function have 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 likely pathogenic.