13-40807405-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_014252.4(SLC25A15):c.564C>T(p.Phe188Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

SLC25A15
NM_014252.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.875

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:

TPTE2P5 (HGNC:42356): (TPTE2 pseudogene 5)

TPTE2P5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 13-40807405-C-T is Benign according to our data. Variant chr13-40807405-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 387375.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr13-40807405-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.875 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A15	NM_014252.4 link	c.564C>T	p.Phe188Phe	synonymous_variant	Exon 5 of 7	ENST00000338625.9	NP_055067.1	Q9Y619
TPTE2P5	NR_038258.1 link	n.623-6681G>A		intron_variant	Intron 7 of 7
TPTE2P5	NR_038259.1 link	n.452-6681G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A15	ENST00000338625.9 link	c.564C>T	p.Phe188Phe	synonymous_variant	Exon 5 of 7	1	NM_014252.4	ENSP00000342267.4		Q9Y619

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000855

AC:

215

AN:

251488

Hom.:

AF XY:

0.000817

AC XY:

111

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00124

AC:

1815

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

849

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152286

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00109

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00142

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Uncertain:1Benign:1

Apr 28, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 02, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.1

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over