ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.106A>T (p.Arg36Ter)

gnomAD frequency: 0.00001  dbSNP: rs1182326570
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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 RCV000502743 SCV000598181 pathogenic Mitochondrial DNA depletion syndrome 13 2017-08-10 criteria provided, single submitter clinical testing The NM_012160.4:c.106A>T (NP_036292.2:p.Arg36Ter) [GRCH38: NC_000006.12:g.98926883T>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:23993194 . 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.
Ambry Genetics RCV000622677 SCV000741865 pathogenic Inborn genetic diseases 2016-10-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001865630 SCV002230782 pathogenic not provided 2021-12-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 437488). This premature translational stop signal has been observed in individual(s) with mitochondrial encephalomyopathy (PMID: 23993194). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg36*) 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).

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