ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1641_1642del (p.Cys547_Asp548delinsTer)

dbSNP: rs765882664
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255233 SCV000321634 pathogenic not provided 2022-02-02 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; This variant is associated with the following publications: (PMID: 26404457, 26968897, 25868664, 27743463, 30831263, 28940506, 30853194, 30679813, 31984159, 32445240)
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000500450 SCV000598194 pathogenic Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter clinical testing The NM_012160.4:c.1641_1642del (NP_036292.2:p.Cys547Ter) [GRCH38: NC_000006.12:g.98875481_98875482del] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:25868664 ; 27743463 . 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. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 13 which is a recessive disorder. PP4:Patient’s phenotype or family history is highly specific for FBXL4. PP5:Reputable source(s) suggest that the variant is pathogenic. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000500450 SCV002072557 pathogenic Mitochondrial DNA depletion syndrome 13 2022-01-20 criteria provided, single submitter clinical testing This variant was identified as homozygous. Parents are both heterozygous Criteria applied: PVS1, PM3, PM2_SUP
Labcorp Genetics (formerly Invitae), Labcorp RCV000255233 SCV003267750 pathogenic not provided 2023-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys547*) 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 (rs765882664, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with mitochondrial DNA depletion syndrome (PMID: 26404457, 31984159). ClinVar contains an entry for this variant (Variation ID: 265143). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000500450 SCV004041091 pathogenic Mitochondrial DNA depletion syndrome 13 2023-02-16 criteria provided, single submitter clinical testing

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