Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001223499 | SCV001395651 | likely pathogenic | Hereditary spastic paraplegia 3A | 2019-10-31 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 373 of the ATL1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATL1 protein. This variant also falls at the last nucleotide of exon 11 of the ATL1 coding sequence, which is part of the consensus splice site for this exon. This variant has been observed to segregate with autosomal recessive spastic paraplegia in a family (Invitae). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |