ClinVar

Description

Variant summary: HBB c.93-3T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes the canonical 5' splicing donor site. Three predict the variant weakens the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2e-05 in 252420 control chromosomes. c.93-3T>G has been reported in the literature in multiple individuals affected with Beta Thalassemia Intermedia (example, Wong_1989, Chiou_1993, Ho_1998, Sinha_2009, Al-Allawi_2014, Hassan_2015, Hussain_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The The ITHANET community portal has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.