rs10252573

Variant names:

• chr7-96145811-T-A
• rs10252573
• NM_014251.3:c.1452+745A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014251.3(SLC25A13):​c.1452+745A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,060 control chromosomes in the GnomAD database, including 10,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10705 hom., cov: 33)
• Consequence: SLC25A13 NM_014251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 publications found

Genes affected

SLC25A13 (HGNC:10983): (solute carrier family 25 member 13) This gene is a member of the mitochondrial carrier family. The encoded protein contains four EF-hand Ca(2+) binding motifs in the N-terminal domain, and localizes to mitochondria. The protein catalyzes the exchange of aspartate for glutamate and a proton across the inner mitochondrial membrane, and is stimulated by calcium on the external side of the inner mitochondrial membrane. Mutations in this gene result in citrullinemia, type II. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

SLC25A13 Gene-Disease associations (from GenCC):

• citrin deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• citrullinemia, type II, adult-onset

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• citrullinemia type II

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neonatal intrahepatic cholestasis due to citrin deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014251.3. 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
	SLC25A13	NM_014251.3	MANE Select	c.1452+745A>T		intron	N/A	NP_055066.1
	SLC25A13	NM_001160210.2		c.1455+745A>T		intron	N/A	NP_001153682.1
	SLC25A13	NR_027662.2		n.1478+745A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.1452+745A>T		intron	N/A	ENSP00000265631.6
	SLC25A13	ENST00000416240.6	TSL:1	c.1455+745A>T		intron	N/A	ENSP00000400101.2
	SLC25A13	ENST00000856215.1		c.1452+745A>T		intron	N/A	ENSP00000526274.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56195 AN: 151942 Hom.: 10690 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.370 AC: 56244 AN: 152060 Hom.: 10705 Cov.: 33 AF XY: 0.372 AC XY: 27681 AN XY: 74318

African (AFR) AF: 0.284 AC: 11786 AN: 41484

American (AMR) AF: 0.389 AC: 5942 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3014 AN: 5172

South Asian (SAS) AF: 0.518 AC: 2499 AN: 4824

European-Finnish (FIN) AF: 0.391 AC: 4120 AN: 10548

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26672 AN: 67962

Other (OTH) AF: 0.395 AC: 834 AN: 2114

Alfa AF: 0.376 Hom.: 1348

Bravo AF: 0.362

Asia WGS AF: 0.552 AC: 1911 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10252573; hg19: chr7-95775123;