13-40793115-TGCTGCAGACTTGGACTAATGGTGAACTCTTGCCTCCCCCCAGGGATATGTGGTGCCTGTCATAAGCTCCAGAGAGCTGCCTTCCACAAGACCAGCAGAAGAGTGGGCAAACATGAAATCCAATCCTGCTATCCAGGCTGCCATTGACCTCACAGCGGGGGCTGCAGGTACAGTCATGTGCCTCATCACCATGTTTCTGTCGTTGATGGATGGTGTATCTGATG-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_014252.4(SLC25A15):c.-69-41_55+58del variant causes a exon loss, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC25A15
NM_014252.4 exon_loss, splice_region
NM_014252.4 exon_loss, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.929
Genes affected
SLC25A15 (HGNC:10985): (solute carrier family 25 member 15) This gene is a member of the mitochondrial carrier family. The encoded protein transports ornithine across the inner mitochondrial membrane from the cytosol to the mitochondrial matrix. The protein is an essential component of the urea cycle, and functions in ammonium detoxification and biosynthesis of the amino acid arginine. Mutations in this gene result in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. There is a pseudogene of this locus on the Y chromosome.[provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-40793115-TGCTGCAGACTTGGACTAATGGTGAACTCTTGCCTCCCCCCAGGGATATGTGGTGCCTGTCATAAGCTCCAGAGAGCTGCCTTCCACAAGACCAGCAGAAGAGTGGGCAAACATGAAATCCAATCCTGCTATCCAGGCTGCCATTGACCTCACAGCGGGGGCTGCAGGTACAGTCATGTGCCTCATCACCATGTTTCTGTCGTTGATGGATGGTGTATCTGATG-T is Pathogenic according to our data. Variant chr13-40793115-TGCTGCAGACTTGGACTAATGGTGAACTCTTGCCTCCCCCCAGGGATATGTGGTGCCTGTCATAAGCTCCAGAGAGCTGCCTTCCACAAGACCAGCAGAAGAGTGGGCAAACATGAAATCCAATCCTGCTATCCAGGCTGCCATTGACCTCACAGCGGGGGCTGCAGGTACAGTCATGTGCCTCATCACCATGTTTCTGTCGTTGATGGATGGTGTATCTGATG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2501791.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SLC25A15 | NM_014252.4 | c.-69-41_55+58del | exon_loss_variant, splice_region_variant | Exon 2 of 7 | ENST00000338625.9 | NP_055067.1 | ||
| SLC25A15 | NM_014252.4 | c.-69-41_55+58del | splice_acceptor_variant, splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant | Exon 2 of 7 | ENST00000338625.9 | NP_055067.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SLC25A15 | ENST00000338625.9 | c.-69-42_55+57del | exon_loss_variant, splice_region_variant | Exon 2 of 7 | 1 | NM_014252.4 | ENSP00000342267.4 | |||
| SLC25A15 | ENST00000338625 | c.-69-42_55+57del | splice_acceptor_variant, splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant | Exon 2 of 7 | 1 | NM_014252.4 | ENSP00000342267.4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome Pathogenic:1
May 08, 2023
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.