Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001201663 | SCV001372745 | uncertain significance | Idiopathic generalized epilepsy | 2019-10-16 | criteria provided, single submitter | clinical testing | This sequence change affects codon 74 of the RBFOX3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RBFOX3 protein. This variant also falls at the last nucleotide of exon 5 of the RBFOX3 coding sequence, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with RBFOX3-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |