Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001208013 | SCV001379383 | pathogenic | Neuropathy, hereditary motor and sensory, type 6B | 2019-06-05 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the SLC25A46 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be in trans (on the opposite chromosome) from a pathogenic variant and to segregate with pontocerebellar hypoplasia in a family (PMID: 28653766). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC25A46 are known to be pathogenic (PMID: 26168012, 26951855, 27543974). For these reasons, this variant has been classified as Pathogenic. |