ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.989C>G (p.Ala330Gly)

dbSNP: rs368886622
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000501853 SCV000598375 uncertain significance Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.989C>G (NP_036292.2:p.Ala330Gly) [GRCH38: NC_000006.12:g.98905540G>C] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Conflicting 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. BP4:Computational evidence/predictors indicate no impact on the FBXL4 structure, function, or protein-protein interaction. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Conflicting Evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV001865632 SCV002223254 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing 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. This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 330 of the FBXL4 protein (p.Ala330Gly). This variant is present in population databases (rs368886622, gnomAD 0.004%). 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: 437672). 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 RCV001865632 SCV002756584 uncertain significance not provided 2022-05-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Ambry Genetics RCV002524377 SCV003563716 uncertain significance Inborn genetic diseases 2021-06-21 criteria provided, single submitter clinical testing The c.989C>G (p.A330G) alteration is located in exon 5 (coding exon 3) of the FBXL4 gene. This alteration results from a C to G substitution at nucleotide position 989, causing the alanine (A) at amino acid position 330 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.