Submissions for variant NM_014252.4(SLC25A15):c.823C>T (p.Arg275Ter)

gnomAD frequency: 0.00006  dbSNP: rs202247807

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000031955	SCV000944588	likely pathogenic	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	2025-01-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg275*) in the SLC25A15 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the SLC25A15 protein. This variant is present in population databases (rs202247807, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (PMID: 16376511, 23430880). ClinVar contains an entry for this variant (Variation ID: 38403). 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 C-terminus of the SLC25A15 protein. Other variant(s) that disrupt this region (p.Glu288Glyfs*3) have been observed in individuals with SLC25A15-related conditions (PMID: 11552031, 12807890). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000031955	SCV002810435	likely pathogenic	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	2024-06-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000031955	SCV004201687	pathogenic	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	2023-06-29	criteria provided, single submitter	clinical testing
Department of Neurology, Zibo Changguo Hospital	RCV000031955	SCV005889688	likely pathogenic	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	2025-01-10	criteria provided, single submitter	clinical testing	PVS1_Moderate, PM3_Strong, PM2_Supporting, PP4
GeneReviews	RCV000031955	SCV000054634	not provided	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome		no assertion provided	literature only
Natera, Inc.	RCV000031955	SCV001453573	likely pathogenic	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	2020-09-16	no assertion criteria provided	clinical testing