NM_014251.3:c.1178-4867T>A

Variant names:

• chr7-96176391-A-T
• rs768172
• NM_014251.3:c.1178-4867T>A

Variant summary

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

The NM_014251.3(SLC25A13):​c.1178-4867T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,060 control chromosomes in the GnomAD database, including 17,405 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 0.46 (17405 hom., cov: 33)
• Consequence: SLC25A13 NM_014251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 6 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3	c.1178-4867T>A		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.1178-4867T>A		intron_variant	Intron 11 of 17	1	NM_014251.3	ENSP00000265631.6

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70091 AN: 151942 Hom.: 17355 Cov.: 33

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.462 AC: 70205 AN: 152060 Hom.: 17405 Cov.: 33 AF XY: 0.464 AC XY: 34504 AN XY: 74330

African (AFR) AF: 0.646 AC: 26813 AN: 41494

American (AMR) AF: 0.399 AC: 6107 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3165 AN: 5168

South Asian (SAS) AF: 0.562 AC: 2709 AN: 4824

European-Finnish (FIN) AF: 0.368 AC: 3876 AN: 10536

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25421 AN: 67966

Other (OTH) AF: 0.444 AC: 936 AN: 2106

Alfa AF: 0.425 Hom.: 1762

Bravo AF: 0.465

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		0.0010
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: rs768172; hg19: chr7-95805703;