Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000500730 | SCV000598346 | pathogenic | Mitochondrial DNA depletion syndrome 13 | 2017-08-10 | criteria provided, single submitter | reference population | The NM_012160.4:c.859-1G>T (NP_036292.2:p.=) [GRCH38: NC_000006.12:g.98905671C>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predcted null variant in FBXL4 where loss of function is a known mechanism of disease. PM2:This variant is absent in key population databases. PP3:Computational evidence/predictors indicate the variant has deleterious effect on FBXL4 structure, function, or protein-protein interaction. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic. |
Invitae | RCV002524376 | SCV002970391 | likely pathogenic | not provided | 2023-03-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FBXL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 437644). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. This variant is present in population databases (rs368965675, gnomAD 0.007%). This sequence change affects an acceptor splice site in intron 4 of the FBXL4 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 FBXL4 are known to be pathogenic (PMID: 23993193, 23993194, 25868664). |