ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1237T>C (p.Tyr413His)

gnomAD frequency: 0.00086  dbSNP: rs138225703
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688866 SCV000816493 uncertain significance Fanconi anemia 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 413 of the FANCM protein (p.Tyr413His). This variant is present in population databases (rs138225703, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast cancer (PMID: 30426508). ClinVar contains an entry for this variant (Variation ID: 568489). 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.
Fulgent Genetics, Fulgent Genetics RCV000763928 SCV000894872 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001535656 SCV001805174 uncertain significance not provided 2023-09-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast, ovarian, or colorectal cancer, and also in unaffected controls (Broderick et al., 2017; Dicks et al., 2017; Schubert et al., 2019; Bhai et al., 2021); This variant is associated with the following publications: (PMID: 30426508, 27713038, 28881617, 34326862)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001535656 SCV002011503 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV001771942 SCV002030206 uncertain significance Spermatogenic failure 28 2021-02-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4 RCV002256466 SCV002527310 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-08 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV004535713 SCV004119874 uncertain significance FANCM-related disorder 2023-12-08 criteria provided, single submitter clinical testing The FANCM c.1237T>C variant is predicted to result in the amino acid substitution p.Tyr413His. This variant, along with a variant in the CHEK2 gene, has been reported in an individual with breast cancer (Index 4, Schubert et al. 2019. PubMed ID: 30426508). This variant is reported in 0.14% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has been interpreted as variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/568489/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001535656 SCV004218714 likely benign not provided 2022-07-13 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535656 SCV001749710 not provided not provided no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 04-02-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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