ClinVar Miner

Submissions for variant NM_014252.4(SLC25A15):c.564C>G (p.Phe188Leu)

dbSNP: rs141028076
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000031951 SCV001215767 pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2023-02-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 188 of the SLC25A15 protein (p.Phe188Leu). This variant is present in population databases (rs141028076, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of SLC25A15-related conditions (PMID: 19242930, 29554876). ClinVar contains an entry for this variant (Variation ID: 38399). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC25A15 protein function. Experimental studies have shown that this missense change affects SLC25A15 function (PMID: 25818551, 26589310). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Phe188 amino acid residue in SLC25A15. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10369256, 12807890, 23430880). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
Centogene AG - the Rare Disease Company RCV000031951 SCV001424487 pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome criteria provided, single submitter clinical testing
Baylor Genetics RCV000031951 SCV004201692 likely pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2022-11-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV000031951 SCV002086772 likely pathogenic Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2020-11-03 no assertion criteria provided clinical testing

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