Submissions for variant NM_014780.5(CUL7):c.3645+1G>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	RCV002510277	SCV002819294	likely pathogenic	3-M syndrome	2022-12-06	criteria provided, single submitter	clinical testing	Variant summary: CUL7 c.3645+1G>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 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 4e-06 in 249076 control chromosomes. c.3645+1G>A has been reported in the literature in at least one homozygous individual affected with Three M Syndrome 1 (e.g. Huber_2009). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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.