ClinVar

Description

Variant summary: RMRP n.10T>C (also known as n.9T>C) alters a conserved nucleotide in the non-coding RNA sequence. The variant allele was found at a frequency of 7.8e-06 in 128842 control chromosomes (gnomAD). The variant, n.10T>C, has been reported in the literature in at least one compound heterozygous individual affected with Cartilage-Hair Hypoplasia, who also carried a second pathogenic variant (Hermanns_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One in silico study analyzing the local structural effects of SNPs using RNA folding algorithms, predicted this variant to have a significant structural effect (Sabarinathan_2012). In addition, a different variant, affecting the same nucleotide, n.10T>A, has been described in a patient affected with Cartilage-Hair hypoplasia (HGMD), further supporting a structural importance for this nucleotide. The following publications have been ascertained in the context of this evaluation (PMID: 16838329, 21956908, 23315997, 17701897, 21396580). No other submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.