NM_014252.4:c.-67A>G

Variant names:

• chr13-40793160-A-G
• rs112276566
• NM_014252.4:c.-67A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014252.4(SLC25A15):​c.-67A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A15 NM_014252.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ornithine translocase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A15	NM_014252.4	MANE Select	c.-67A>G		splice_region	Exon 2 of 7	NP_055067.1	Q9Y619
	SLC25A15	NM_014252.4	MANE Select	c.-67A>G		5_prime_UTR	Exon 2 of 7	NP_055067.1	Q9Y619

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A15	ENST00000338625.9	TSL:1 MANE Select	c.-67A>G		splice_region	Exon 2 of 7	ENSP00000342267.4	Q9Y619
	SLC25A15	ENST00000338625.9	TSL:1 MANE Select	c.-67A>G		5_prime_UTR	Exon 2 of 7	ENSP00000342267.4	Q9Y619
	SLC25A15	ENST00000707033.1		c.-67A>G		splice_region	Exon 2 of 7	ENSP00000516711.1	Q9Y619

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		-0.35
PromoterAI		-0.0037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs112276566; hg19: chr13-41367296;