Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000500686 | SCV000598357 | uncertain significance | Mitochondrial DNA depletion syndrome 13 | 2017-08-10 | criteria provided, single submitter | reference population | The NM_012160.4:c.913C>G (NP_036292.2:p.Gln305Glu) [GRCH38: NC_000006.12:g.98905616G>C] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Insufficient Evidence based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Insufficient Evidence. |
Neuberg Centre For Genomic Medicine, |
RCV000500686 | SCV005061017 | uncertain significance | Mitochondrial DNA depletion syndrome 13 | criteria provided, single submitter | clinical testing | The observed missense c.913C>G (p.Gln305Glu) variant in FBXL4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gln305Glu variant is reported with allele frequency of 0.002% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. The amino acid change p.Gln305Glu in FBXL4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gln at position 305 is changed to a Glu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |