ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1046T>C (p.Ile349Thr)

gnomAD frequency: 0.00002  dbSNP: rs150185654
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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 RCV001207878 SCV001379245 uncertain significance Fanconi anemia 2023-10-18 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 349 of the FANCM protein (p.Ile349Thr). This variant is present in population databases (rs150185654, gnomAD 0.2%). 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: 938619). 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 threonine 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.
Baylor Genetics RCV001292998 SCV001481722 uncertain significance Spermatogenic failure 28 2020-12-01 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001569260 SCV001793300 uncertain significance not provided 2024-10-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in a childhood patient with acute lymphoblastic leukemia (PMID: 38093606); This variant is associated with the following publications: (PMID: 38093606)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001569260 SCV004218703 uncertain significance not provided 2022-09-07 criteria provided, single submitter clinical testing To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0016 (54/34548 chromosomes in Latino/Admixed American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. 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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