ClinVar Miner

Submissions for variant NM_001191061.2(SLC25A22):c.874G>A (p.Ala292Thr)

gnomAD frequency: 0.00001  dbSNP: rs369729483
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189332 SCV000242967 uncertain significance not provided 2012-08-10 criteria provided, single submitter clinical testing p.Ala292Thr (GCG>ACG):c.874 G>A in exon 10 of the SLC25A22 gene (NM_024698.4). The Ala292Thr missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Ala292Thr in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a non-polar Alanine residue is replaced by a polar Threonine residue. It alters a position in the sixth transmembrane region of the protein that is conserved across species, although a Threonine residue is present at this position in primates. Multiple in silico algorithms predict the Ala292Thr may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Ala292Thr is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001235057 SCV001407721 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 292 of the SLC25A22 protein (p.Ala292Thr). This variant is present in population databases (rs369729483, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC25A22-related conditions. ClinVar contains an entry for this variant (Variation ID: 207173). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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