Submissions for variant NM_001164277.2(SLC37A4):c.148+2T>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	RCV002282846	SCV002570691	likely pathogenic	Glucose-6-phosphate transport defect	2022-07-12	criteria provided, single submitter	clinical testing	Variant summary: SLC37A4 c.148+2T>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. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 247574 control chromosomes (gnomAD). To our knowledge, no occurrence of c.148+2T>A in individuals affected with Glycogen Storage Disease Type Ib and no experimental evidence demonstrating its impact on protein function have been reported. Other loss of function variants in SLC37A4 have been classified as pathogenic in ClinVar and is associated with Glycogen Storage Disease in HGMD. 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.