ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.752A>G (p.Tyr251Cys)

gnomAD frequency: 0.00006  dbSNP: rs758776562
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000503672 SCV000598333 uncertain significance Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.752A>G (NP_036292.2:p.Tyr251Cys) [GRCH38: NC_000006.12:g.98917480T>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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857191 SCV002223301 uncertain significance not provided 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 251 of the FBXL4 protein (p.Tyr251Cys). This variant is present in population databases (rs758776562, gnomAD 0.04%). 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: 437631). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FBXL4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001857191 SCV002567475 uncertain significance not provided 2022-02-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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