Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001054372 | SCV001218682 | pathogenic | Citrin deficiency | 2022-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 33497767). ClinVar contains an entry for this variant (Variation ID: 850244). Disruption of this splice site has been observed in individual(s) with clinical features of citrin deficiency (PMID: 33497767). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 14 of the SLC25A13 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 10369257, 14680984, 27405544). |
Department of Pediatrics, |
RCV001376648 | SCV001442532 | pathogenic | Neonatal intrahepatic cholestasis due to citrin deficiency | 2020-09-01 | criteria provided, single submitter | research | |
Prevention |
RCV003405262 | SCV004109401 | pathogenic | SLC25A13-related condition | 2022-12-03 | criteria provided, single submitter | clinical testing | The SLC25A13 c.1453-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in the compound heterozygous state in an individual with neonatal intrahepatic cholestasis (Lin et al 2021. PubMed ID: 33497767). Functional studies using the minigene assay showed that this variant causes an aberrant transcript leading to a frameshift and premature protein termination (p.Gly485Valfs*22) (Lin et al 2021. PubMed ID: 33497767). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in SLC25A13 are expected to be pathogenic. This variant is interpreted as pathogenic. |