ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1760T>C (p.Ile587Thr)

gnomAD frequency: 0.00007  dbSNP: rs147805461
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000326638 SCV001237299 uncertain significance Fanconi anemia 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 587 of the FANCM protein (p.Ile587Thr). This variant is present in population databases (rs147805461, gnomAD 0.05%). 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: 313201). 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 RCV001552736 SCV001773480 uncertain significance not provided 2024-07-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34326862, 28881617, 28678401)
Fulgent Genetics, Fulgent Genetics RCV002480131 SCV002775890 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2021-07-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001552736 SCV004218726 uncertain significance not provided 2023-08-04 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in individuals with head and neck squamous cell carcinoma (HNSCC) (PMID: 28678401 (2017)), and in individuals with personal and/or family history of cancer (PMID: 34326862 (2021)). This variant is also reported in unaffected individuals (PMID: 28881617 (2017)). The frequency of this variant in the general population, 0.00048 (17/35304 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.

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