Submissions for variant NM_000382.3(ALDH3A2):c.471+1G>C

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	RCV001255500	SCV001431928	pathogenic	Sjögren-Larsson syndrome	2020-08-27	criteria provided, single submitter	clinical testing	Variant summary: ALDH3A2 c.471+1G>C 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. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. These predictions have been confirmed by functional study that demonstrated an in-frame deletion of exon 2 and 3 in a patient derived mRNA sample (Kraus_2000). The variant allele was found at a frequency of 4e-06 in 251416 control chromosomes (gnomAD). The variant, c.471+1G>C, has been reported in the literature in a compound heterozygous individual affected with Sjogren-Larsson Syndrome (Kraus_2000). This publication also evaluated the impact of the variant at the protein level, and demonstrated a significantly shortened protein product in a protein truncation test (Kraus_2000). 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 pathogenic.