Description
Variant summary: POMT1 c.765+19C>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. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant causes a missense change in an alternate transcript (NM_001374689.1: c.622C>G, p.Pro208Ala). The variant allele was found at a frequency of 8e-05 in 250846 control chromosomes (gnomAD). This frequency is not higher than estimated for a pathogenic variant in POMT1 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (8e-05 vs 0.00072), allowing no conclusion about variant significance. To our knowledge, no occurrence of the variant in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
