13-40789474-G-C

Position:

• chr13-40789474-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000707033(SLC25A15):​c.-259G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 151,404 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (247 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: SLC25A15 ENST00000707033 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 13-40789474-G-C is Benign according to our data. Variant chr13-40789474-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 312170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.40789474G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A15	ENST00000707033	c.-259G>C		5_prime_UTR_variant	1/7			ENSP00000516711.1
SLC25A15	ENST00000478827.1	n.63G>C		non_coding_transcript_exon_variant	1/7	5

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5464 AN: 151254 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.00723

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.0293

GnomAD4 exome AF: 0.0714 AC: 3 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 3 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0625

GnomAD4 genome AF: 0.0364 AC: 5511 AN: 151362 Hom.: 247 Cov.: 32 AF XY: 0.0410 AC XY: 3030 AN XY: 73972

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.00723

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.00556

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0208 Hom.: 6

Asia WGS AF: 0.177 AC: 569 AN: 3232

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2021

- -

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.1
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs191621874; hg19: chr13-41363610;