ClinVar

Description

Variant summary: HBB c.16C>T (p.Pro6Ser) results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251132 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.16C>T has been reported in the literature in at least one compound heterozygous individual affected with Hemoglobinopathy (Kayisli_2005). The variant was also reported in a severely anemic patient with a truncating variant in cis and a pathogenic splice variant in trans (Agarwal_1997). 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. Three ClinVar submitters have assessed the variant since 2014: all classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.