ClinVar Miner

Submissions for variant NM_138773.4(SLC25A46):c.314T>C (p.Ile105Thr)

gnomAD frequency: 0.00003  dbSNP: rs375056013
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001037605 SCV001201029 uncertain significance Neuropathy, hereditary motor and sensory, type 6B 2022-05-31 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 105 of the SLC25A46 protein (p.Ile105Thr). This variant is present in population databases (rs375056013, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. ClinVar contains an entry for this variant (Variation ID: 836468). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001508523 SCV001714735 uncertain significance not provided 2020-07-16 criteria provided, single submitter clinical testing
GeneDx RCV001508523 SCV002552930 uncertain significance not provided 2022-01-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002320239 SCV002608605 uncertain significance Inborn genetic diseases 2021-04-14 criteria provided, single submitter clinical testing The p.I105T variant (also known as c.314T>C), located in coding exon 2 of the SLC25A46 gene, results from a T to C substitution at nucleotide position 314. The isoleucine at codon 105 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV001508523 SCV004159199 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing SLC25A46: PM2

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