ClinVar Miner

Submissions for variant NM_152269.5(MTRFR):c.433G>A (p.Ala145Thr)

gnomAD frequency: 0.00001  dbSNP: rs749208492
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848361 SCV002106301 uncertain significance Hereditary spastic paraplegia 2017-02-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002236181 SCV002509580 uncertain significance Combined oxidative phosphorylation defect type 7; Spastic paraplegia 2022-07-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1344258). This variant has not been reported in the literature in individuals affected with C12orf65-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 145 of the C12orf65 protein (p.Ala145Thr).
PreventionGenetics, part of Exact Sciences RCV003976236 SCV004789226 uncertain significance MTRFR-related disorder 2023-12-19 no assertion criteria provided clinical testing The MTRFR c.433G>A variant is predicted to result in the amino acid substitution p.Ala145Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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