Submissions for variant NM_001195248.2(APTX):c.-5+1G>T

gnomAD frequency: 0.00062  dbSNP: rs146487634

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000999150	SCV001155627	likely pathogenic	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003396584	SCV004122906	uncertain significance	not specified	2023-10-13	criteria provided, single submitter	clinical testing	Variant summary: APTX c.-111+1G>T is located in a canonical splice-site in the 5'UTR region 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 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 0.00013 in 251034 control chromosomes. To our knowledge, no occurrence of c.-111+1G>T in individuals affected with Ataxia, Early-Onset, With Oculomotor Apraxia And Hypoalbuminemia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.