Description
Variant summary: TBCE c.100+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site, while three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-05 in 249900 control chromosomes (gnomAD). This frequency allows no conclusions about variant significance. The variant, c.100+1G>A, has been reported in the literature in a homozygous individual affected with TBCE-Related Disorder (Globa_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and reported the variant with conflicting assessments (VUS (n=2), likely pathogenic (n=2)). Based on the evidence outlined above, the variant was classified as likely pathogenic.
| # | 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 |
