ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.3998A>C (p.Gln1333Pro)

gnomAD frequency: 0.00007  dbSNP: rs143681767
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000275476 SCV001413493 uncertain significance Fanconi anemia 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1333 of the FANCM protein (p.Gln1333Pro). This variant is present in population databases (rs143681767, gnomAD 0.02%). 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: 313213). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV001564652 SCV001787849 uncertain significance not provided 2024-06-06 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in individuals with breast, colorectal, or ovarian cancer, but also in unaffected controls (PMID: 27713038, 28881617, 36315097); This variant is associated with the following publications: (PMID: 27713038, 28881617, 27363283, 36315097)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001564652 SCV005626298 uncertain significance not provided 2024-07-01 criteria provided, single submitter clinical testing The FANCM c.3998A>C (p.Gln1333Pro) variant has been reported in the published literature in individuals with breast cancer and in reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/FANCM)). Additionally, this variant has been seen in individuals over the age of 70 who have not developed cancer (FLOSSIES, https://whi.color.com/). The frequency of this variant in the general population, 0.00025 (32/126186 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this 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.