Submissions for variant NM_018075.5(ANO10):c.1293+1G>T

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	RCV004800025	SCV005423026	likely pathogenic	Autosomal recessive spinocerebellar ataxia 10	2024-10-07	criteria provided, single submitter	clinical testing	Variant summary: ANO10 c.1293+1G>T 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 ANO10 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 allele was found at a frequency of 2.5e-06 in 1574512 control chromosomes. To our knowledge, no occurrence of c.1293+1G>T in individuals affected with Spinocerebellar ataxia 10 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.