7-96171508-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014251.3(SLC25A13):c.1194A>G(p.Leu398Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,607,950 control chromosomes in the GnomAD database, including 116,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9459 hom., cov: 32)

Exomes 𝑓: 0.38 ( 107173 hom. )

Consequence

SLC25A13
NM_014251.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:10

Conservation

PhyloP100: 0.616

Publications

30 publications found

Variant links:

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

SLC25A13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-96171508-T-C is Benign according to our data. Variant chr7-96171508-T-C is described in ClinVar as Benign. ClinVar VariationId is 260370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.616 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3 link	c.1194A>G	p.Leu398Leu	synonymous_variant	Exon 12 of 18	ENST00000265631.10	NP_055066.1	Q9UJS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A13	ENST00000265631.10 link	c.1194A>G	p.Leu398Leu	synonymous_variant	Exon 12 of 18	1	NM_014251.3	ENSP00000265631.6		Q9UJS0-1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52262

AN:

151896

Hom.:

9434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.530

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.355

GnomAD2 exomes

AF:

0.395

AC:

99124

AN:

250830

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.377

AC:

549070

AN:

1455936

Hom.:

107173

Cov.:

AF XY:

0.382

AC XY:

276889

AN XY:

724604

show subpopulations

African (AFR)

AF:

0.250

AC:

8338

AN:

33388

American (AMR)

AF:

0.377

AC:

16873

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6898

AN:

26100

East Asian (EAS)

AF:

0.568

AC:

22511

AN:

39634

South Asian (SAS)

AF:

0.535

AC:

46035

AN:

86110

European-Finnish (FIN)

AF:

0.377

AC:

20101

AN:

53316

Middle Eastern (MID)

AF:

0.414

AC:

2377

AN:

5746

European-Non Finnish (NFE)

AF:

0.364

AC:

403001

AN:

1106760

Other (OTH)

AF:

0.381

AC:

22936

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

14830

29660

44491

59321

74151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12794

25588

38382

51176

63970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.344

AC:

52317

AN:

152014

Hom.:

9459

Cov.:

AF XY:

0.349

AC XY:

25911

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.255

AC:

10571

AN:

41452

American (AMR)

AF:

0.353

AC:

5403

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

896

AN:

3468

East Asian (EAS)

AF:

0.591

AC:

3059

AN:

5172

South Asian (SAS)

AF:

0.530

AC:

2546

AN:

4802

European-Finnish (FIN)

AF:

0.362

AC:

3825

AN:

10554

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25000

AN:

67962

Other (OTH)

AF:

0.362

AC:

765

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1733

3466

5200

6933

8666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.361

Hom.:

45193

Bravo

AF:

0.335

Asia WGS

AF:

0.559

AC:

1944

AN:

3478

EpiCase

AF:

0.361

EpiControl

AF:

0.360

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

Allele frequency is common in at least one population database (frequency: 57.961% in ExAC) based on the frequency threshold of 1.504% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. 4 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. A synonymous variant not located in a splice region. -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 07, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neonatal intrahepatic cholestasis due to citrin deficiency

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Citrin deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Citrullinemia type II

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Citrullinemia, type II, adult-onset

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Late-onset citrullinemia

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Citrullinemia type I

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

(source)

DANN

Benign

0.73

PhyloP100

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over