ClinVar Miner

Submissions for variant NM_005262.3(GFER):c.199del (p.Arg67fs)

dbSNP: rs863224028
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200750 SCV000251540 likely pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing c.199delC:p.Arg67GlyfsX83 (R67GfsX83) in exon 1 of the GFER gene (NM_005262.2). The normal sequence with the base that is deleted in braces is: CTCC{C}GGAG. The c.199delC variant in the GFER gene causes a frameshift starting with codon Arginine 67, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 83 of the new reading frame, denoted p.Arg67GlyfsX83. It has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay; however, to date no frameshift variants have been reported in the GFER gene. The c.199delC variant is a good candidate for a pathogenic variant, but the possibility it may be a rare benign variant cannot be excluded.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270124 SCV001448990 likely pathogenic Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome 2017-07-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000200750 SCV004665080 uncertain significance not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg67Glyfs*83) in the GFER gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 139 amino acid(s) of the GFER protein. This variant is present in population databases (rs747241374, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of GFER-related condition (PMID: 34732400). ClinVar contains an entry for this variant (Variation ID: 214476). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Wellcome Centre for Mitochondrial Research, Newcastle University RCV000508880 SCV000575905 pathogenic Mitochondrial disease 2017-04-07 no assertion criteria provided clinical testing

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