ClinVar

Description

Variant summary: ASS1 c.-5-10C>G is located in the untranslated mRNA region upstream of the initiation codon. Several computational tools predict a significant impact on normal splicing: two predict the variant abolishes a 3 prime acceptor site; one predicts the variant weakens a 3 prime acceptor site; one predicts the variant creates a 3 prime acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 249576 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-5-10C>G has been reported in the literature in an individual (compound heterozygote) affected with Citrullinemia Type I (Fernandez-Carmen Diez_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.