ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1301T>C (p.Ile434Thr)

gnomAD frequency: 0.00001  dbSNP: rs763653491
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462412 SCV000547796 uncertain significance Fanconi anemia 2023-12-12 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 434 of the FANCM protein (p.Ile434Thr). This variant is present in population databases (rs763653491, gnomAD 0.1%). 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: 408218). 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.
GeneDx RCV002291631 SCV002584228 uncertain significance not provided 2023-07-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002480396 SCV002780311 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-04-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002526414 SCV003697427 uncertain significance Inborn genetic diseases 2021-09-17 criteria provided, single submitter clinical testing The c.1301T>C (p.I434T) alteration is located in exon 7 (coding exon 7) of the FANCM gene. This alteration results from a T to C substitution at nucleotide position 1301, causing the isoleucine (I) at amino acid position 434 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002291631 SCV004218717 uncertain significance not provided 2023-06-13 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0011 (38/34234 chromosomes in Latino/Admixed American subpopulation (Genome Aggregation Database, 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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