ClinVar Miner

Submissions for variant NM_005262.3(GFER):c.586C>T (p.Arg196Cys)

gnomAD frequency: 0.00007  dbSNP: rs370475970
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000709773 SCV002767524 uncertain significance Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome 2020-05-25 criteria provided, single submitter clinical testing A heterozygous missense variant was identified, NM_005262.2(GFER):c.586C>T in exon 3 of 3 of the GFER gene. This substitution is predicted to create a major amino acid change from an arginine to a cysteine at position 196 of the protein; NP_005253.3(GFER):p.(Arg196Cys). The arginine at this position has high conservation (100 vertebrates, UCSC), and is located within the Erv1 / Alr family domain (NCBI, PDB). In silico software predicts this variant to be damaging (PolyPhen2, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a global population frequency of 0.004% (10 heterozygotes; 0 homozygotes) with a Latino sub-population frequency of 0.008%. An alternative residue change to histidine at the same location has also been reported in the gnomAD database at a frequency of 0.01%. This variant has been previously reported as pathogenic in a patient with mitochondrial disease (ClinVar, Martikainen, M. et al. (2017)). Based on information available at the time of curation, this variant has been classified as a VUS with POTENTIAL CLINICAL RELEVANCE.
Wellcome Centre for Mitochondrial Research, Newcastle University RCV000508691 SCV000575906 pathogenic Mitochondrial disease 2017-04-07 no assertion criteria provided clinical testing
GenomeConnect, ClinGen RCV000709773 SCV000840091 not provided Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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.