ClinVar Miner

Submissions for variant NM_014252.4(SLC25A15):c.147C>G (p.Asp49Glu)

gnomAD frequency: 0.00009  dbSNP: rs187685447
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000877375 SCV001020105 likely benign Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000877375 SCV001269009 uncertain significance Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Natera, Inc. RCV000877375 SCV001454137 uncertain significance Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 2020-04-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356738 SCV001551991 uncertain significance not provided no assertion criteria provided clinical testing The SLC25A15 p.Asp49Glu variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs187685447) and in control databases in 62 of 282886 chromosomes (2 homozygous) at a frequency of 0.000219 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 53 of 19952 chromosomes (freq: 0.002656), Other in 2 of 7228 chromosomes (freq: 0.000277), South Asian in 6 of 30616 chromosomes (freq: 0.000196) and Latino in 1 of 35438 chromosomes (freq: 0.000028), but was not observed in the African, Ashkenazi Jewish, European (Finnish) or European (non-Finnish) populations. The p.Asp49 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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