ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1288C>T (p.Arg430Ter)

gnomAD frequency: 0.00003  dbSNP: rs758395213
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Total submissions: 6
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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 RCV000503988 SCV000598428 likely pathogenic Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter reference population The NM_012160.4:c.1288C>T (NP_036292.2:p.Arg430Ter) [GRCH38: NC_000006.12:g.98899297G>A] variant in FBXL4 gene is interpretated to be a Likely 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. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Likely Pathogenic.
Mendelics RCV000503988 SCV001137197 pathogenic Mitochondrial DNA depletion syndrome 13 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001857195 SCV002129352 pathogenic not provided 2023-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg430*) in the FBXL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBXL4 are known to be pathogenic (PMID: 23993193, 23993194, 25868664). This variant is present in population databases (rs758395213, gnomAD 0.007%). 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: 437724). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001857195 SCV002765392 likely pathogenic not provided 2022-06-14 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV000503988 SCV002806094 likely pathogenic Mitochondrial DNA depletion syndrome 13 2021-10-08 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV000503988 SCV001760192 likely pathogenic Mitochondrial DNA depletion syndrome 13 no assertion criteria provided clinical testing

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