ClinVar Miner

Submissions for variant NM_014252.4(SLC25A15):c.95C>G (p.Thr32Arg)

dbSNP: rs121908536
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000006366 SCV001443691 pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2019-12-11 criteria provided, single submitter clinical testing This variant has been previously reported as a homozygous change in patients with Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (PMID: 16940241). In vitro overexpression studies of this variant showed that it diminished but does not completely abolish SLC25A15 protein function (PMID: 16940241). Additional studies using fibroblasts from patients carrying this variant in the homozygous state also showed a reduction in protein function (PMID: 16940241). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.95C>G (p.Thr32Arg) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.95C>G (p.Thr32Arg) variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000006366 SCV003442208 pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2022-05-30 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SLC25A15 function (PMID: 16940241). 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"). ClinVar contains an entry for this variant (Variation ID: 6000). This missense change has been observed in individual(s) with HHH syndrome (PMID: 16940241). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 32 of the SLC25A15 protein (p.Thr32Arg).
OMIM RCV000006366 SCV000026548 pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2006-10-01 no assertion criteria provided literature only
GeneReviews RCV000006366 SCV000054637 not provided Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome no assertion provided literature only

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