ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.3731A>G (p.Glu1244Gly)

gnomAD frequency: 0.00006  dbSNP: rs746030136
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686815 SCV000814351 uncertain significance Fanconi anemia 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1244 of the FANCM protein (p.Glu1244Gly). This variant is present in population databases (rs746030136, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 566886). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV000767965 SCV001805238 uncertain significance not provided 2024-03-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with ovarian cancer as well as unaffected controls (PMID: 28881617); This variant is associated with the following publications: (PMID: 28881617)
Fulgent Genetics, Fulgent Genetics RCV002485604 SCV002792785 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2021-10-15 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002485604 SCV003919938 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2021-03-30 criteria provided, single submitter clinical testing FANCM NM_020937.3 exon 14 p.Glu1244Gly (c.3731A>G): This variant has not been reported in the literature but is present in 3/125158 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs746030136). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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.