rs2375044

Variant names:

• chr7-96177826-A-G
• rs2375044
• NM_014251.3:c.1178-6302T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-96177826-A-G
• chr7-96177826-A-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.1178-6302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,932 control chromosomes in the GnomAD database, including 14,020 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 0.42 (14020 hom., cov: 32)
• Consequence: SLC25A13 NM_014251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3	c.1178-6302T>C		intron_variant	Intron 11 of 17	ENST00000265631.10	NP_055066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A13	ENST00000265631.10	c.1178-6302T>C		intron_variant	Intron 11 of 17	1	NM_014251.3	ENSP00000265631.6

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64080 AN: 151814 Hom.: 13979 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.422 AC: 64181 AN: 151932 Hom.: 14020 Cov.: 32 AF XY: 0.425 AC XY: 31583 AN XY: 74268

African (AFR) AF: 0.509 AC: 21101 AN: 41430

American (AMR) AF: 0.386 AC: 5889 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3466

East Asian (EAS) AF: 0.612 AC: 3167 AN: 5172

South Asian (SAS) AF: 0.562 AC: 2701 AN: 4810

European-Finnish (FIN) AF: 0.368 AC: 3879 AN: 10542

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.374 AC: 25379 AN: 67936

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.390 Hom.: 4812

Bravo AF: 0.421

Asia WGS AF: 0.605 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.52
PhyloP100		-0.60
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: rs2375044; hg19: chr7-95807138;