ClinVar Miner

Submissions for variant NM_024996.7(GFM1):c.139C>T (p.Arg47Ter)

gnomAD frequency: 0.00002  dbSNP: rs119470019
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001207728 SCV001379093 pathogenic not provided 2023-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg47*) in the GFM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GFM1 are known to be pathogenic (PMID: 16632485, 17160893). This variant is present in population databases (rs119470019, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with GFM1-related conditions (PMID: 17160893). ClinVar contains an entry for this variant (Variation ID: 4161). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004378 SCV004121768 pathogenic Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 2023-10-17 criteria provided, single submitter clinical testing Variant summary: GFM1 c.139C>T (p.Arg47X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 251442 control chromosomes. c.139C>T has been reported in the literature in at least one compound heterozygous individual affected with early-onset Leigh syndrome with evidence of familial co-segregation (e.g.Valente_2007). One publication reports experimental evidence evaluating an impact on protein function, however, does not provide sufficient evidence about the variant effect (e.g.Valente_2007). The following publication has been ascertained in the context of this evaluation (PMID: 17160893). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000004378 SCV004199321 pathogenic Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 2023-07-14 criteria provided, single submitter clinical testing
OMIM RCV000004378 SCV000024550 pathogenic Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 2007-01-01 no assertion criteria provided literature only
Natera, Inc. RCV000004378 SCV002081585 pathogenic Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 2020-03-02 no assertion criteria provided clinical testing

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