Variant 13-40793115-TGCTGCAGACTTGGACTAATGGTGAACTCTTGCCTCCCCCCAGGGATATGTGGTGCCTGTCATAAGCTCCAGAGAGCTGCCTTCCACAAGACCAGCAGAAGAGTGGGCAAACATGAAATCCAATCCTGCTATCCAGGCTGCCATTGACCTCACAGCGGGGGCTGCAGGTACAGTCATGTGCCTCATCACCATGTTTCTGTCGTTGATGGATGGTGTATCTGATG-T details in Genebe, Genetics Data Aggregator

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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.929

Variant links:

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]

SLC25A15 links:

SLC25A15 (HGNC:):

SLC25A15 links:

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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/exons	MANE	Protein	UniProt
SLC25A15	NM_014252.4 linkuse as main transcript	c.-69-41_55+58del		exon_loss_variant, splice_region_variant	2/7	ENST00000338625.9	NP_055067.1	Q9Y619
SLC25A15	NM_014252.4 linkuse as main transcript	c.-69-41_30+83del		splice_acceptor_variant, splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant	2/7	ENST00000338625.9	NP_055067.1	Q9Y619

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A15	ENST00000338625.9 linkuse as main transcript	c.-69-41_55+58del		exon_loss_variant, splice_region_variant	2/7	1	NM_014252.4	ENSP00000342267.4		Q9Y619
SLC25A15	ENST00000338625 linkuse as main transcript	c.-69-41_30+83del		splice_acceptor_variant, splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant	2/7	1	NM_014252.4	ENSP00000342267.4		Q9Y619

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

May 08, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.