ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.493A>C (p.Asn165His)

gnomAD frequency: 0.00001  dbSNP: rs761003289
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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 RCV000500748 SCV000598286 uncertain significance Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.493A>C (NP_036292.2:p.Asn165His) [GRCH38: NC_000006.12:g.98926496T>G] 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 RCV002524365 SCV002999566 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 165 of the FBXL4 protein (p.Asn165His). This variant is present in population databases (rs761003289, gnomAD 0.003%). 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: 437584). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002524364 SCV003599177 uncertain significance Inborn genetic diseases 2022-02-02 criteria provided, single submitter clinical testing The c.493A>C (p.N165H) alteration is located in exon 3 (coding exon 1) of the FBXL4 gene. This alteration results from a A to C substitution at nucleotide position 493, causing the asparagine (N) at amino acid position 165 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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