ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.1635_1636TG[3] (p.Cys547_Asp548delinsTer) (rs765882664)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255233 SCV000321634 pathogenic not provided 2017-03-28 criteria provided, single submitter clinical testing The c.1641_1642delTG variant in the FBXL4 gene has been reported previously in association with encephalomyopathic mitochondrial DNA depletion syndrome, when present in the homozygous state or when in trans with another pathogenic variant (Antoun et al., 2015; Huemer et al., 2015). The c.1641_1642delTG variant causes a frameshift starting with codon Cysteine 547, and changes this amino acid to a premature Stop codon, denoted p.Cys547Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1641_1642delTG variant is observed in 3/10,404 (0.03%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). We interpret c.1641_1642delTG as a pathogenic variant.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000500450 SCV000598194 pathogenic Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) 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.

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.