ClinVar Miner

Submissions for variant NM_138773.4(SLC25A46):c.742A>C (p.Ile248Leu)

gnomAD frequency: 0.00191  dbSNP: rs149585060
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493127 SCV000582168 uncertain significance not provided 2017-05-11 criteria provided, single submitter clinical testing The I248L variant in the SLC25A46 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I248L variant is observed in 61/10404 (0.58%) alleles from individuals of Afrcian background, in the ExAC dataset (Lek et al., 2016). The I248L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I248L as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001080440 SCV001015727 likely benign Neuropathy, hereditary motor and sensory, type 6B 2024-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002383946 SCV002671313 likely benign Inborn genetic diseases 2019-11-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV003902745 SCV004727347 likely benign SLC25A46-related disorder 2019-11-21 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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