chr13-40789459-T-C

Variant names:

• chr13-40789459-T-C
• rs7997189
• ENST00000478827.1:n.48T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000478827.1(SLC25A15):​n.48T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,382 control chromosomes in the GnomAD database, including 24,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24182 hom., cov: 34)
  • Exomes 𝑓: 0.33 (7 hom.)
• Consequence: SLC25A15 ENST00000478827.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.152
• Publications: 5 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 13-40789459-T-C is Benign according to our data. Variant chr13-40789459-T-C is described in ClinVar as Benign. ClinVar VariationId is 312168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478827.1. 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.-274T>C		upstream_gene	N/A	NP_055067.1	Q9Y619

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A15	ENST00000478827.1	TSL:5	n.48T>C		non_coding_transcript_exon	Exon 1 of 7
	SLC25A15	ENST00000338625.9	TSL:1 MANE Select	c.-274T>C		upstream_gene	N/A	ENSP00000342267.4	Q9Y619
	SLC25A15	ENST00000707033.1		c.-274T>C		upstream_gene	N/A	ENSP00000516711.1	Q9Y619

Frequencies

GnomAD3 genomes AF: 0.562 AC: 84988 AN: 151164 Hom.: 24144 Cov.: 34

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.327 AC: 36 AN: 110 Hom.: 7 Cov.: 0 AF XY: 0.341 AC XY: 30 AN XY: 88

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.298 AC: 28 AN: 94

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.562 AC: 85078 AN: 151272 Hom.: 24182 Cov.: 34 AF XY: 0.566 AC XY: 41821 AN XY: 73908

African (AFR) AF: 0.631 AC: 26129 AN: 41418

American (AMR) AF: 0.602 AC: 9162 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2008 AN: 3466

East Asian (EAS) AF: 0.584 AC: 3003 AN: 5138

South Asian (SAS) AF: 0.483 AC: 2332 AN: 4828

European-Finnish (FIN) AF: 0.579 AC: 5934 AN: 10250

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.509 AC: 34458 AN: 67656

Other (OTH) AF: 0.597 AC: 1256 AN: 2104

Alfa AF: 0.377 Hom.: 923

Bravo AF: 0.570

Asia WGS AF: 0.557 AC: 1860 AN: 3338

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.4
DANN	Benign	0.17
PhyloP100		0.15
PromoterAI		-0.0042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7997189; hg19: chr13-41363595;