NM_014251.3:c.328+6A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014251.3(SLC25A13):c.328+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,608,688 control chromosomes in the GnomAD database, including 329,405 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34153 hom., cov: 31)

Exomes 𝑓: 0.63 ( 295252 hom. )

Consequence

SLC25A13
NM_014251.3 splice_region, intron

Scores

Splicing: ADA: 0.00009214

Clinical Significance

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

Conservation

PhyloP100: -0.323

Publications

19 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), PanelApp Australia
neonatal intrahepatic cholestasis due to citrin deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet
citrullinemia type II
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-96234796-T-C is Benign according to our data. Variant chr7-96234796-T-C is described in ClinVar as Benign. ClinVar VariationId is 260371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A13	NM_014251.3	MANE Select	c.328+6A>G	splice_region intron	N/A	NP_055066.1	Q9UJS0-1
SLC25A13	NM_001160210.2		c.328+6A>G	splice_region intron	N/A	NP_001153682.1	Q9UJS0-2
SLC25A13	NR_027662.2		n.355-25819A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.328+6A>G	splice_region intron	N/A	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6	TSL:1	c.328+6A>G	splice_region intron	N/A	ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000856215.1		c.328+6A>G	splice_region intron	N/A	ENSP00000526274.1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101194

AN:

151708

Hom.:

34132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.658

GnomAD2 exomes

AF:

0.616

AC:

154731

AN:

251160

AF XY:

0.607

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.645

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.633

AC:

922545

AN:

1456882

Hom.:

295252

Cov.:

AF XY:

0.628

AC XY:

455201

AN XY:

725054

show subpopulations

African (AFR)

AF:

0.750

AC:

25020

AN:

33354

American (AMR)

AF:

0.628

AC:

28065

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.744

AC:

19404

AN:

26084

East Asian (EAS)

AF:

0.463

AC:

18351

AN:

39618

South Asian (SAS)

AF:

0.460

AC:

39602

AN:

86152

European-Finnish (FIN)

AF:

0.640

AC:

34126

AN:

53300

Middle Eastern (MID)

AF:

0.588

AC:

3385

AN:

5758

European-Non Finnish (NFE)

AF:

0.647

AC:

716452

AN:

1107704

Other (OTH)

AF:

0.633

AC:

38140

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

16614

33228

49842

66456

83070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18766

37532

56298

75064

93830

<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:

0.667

AC:

101251

AN:

151806

Hom.:

34153

Cov.:

AF XY:

0.662

AC XY:

49059

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.750

AC:

31085

AN:

41458

American (AMR)

AF:

0.650

AC:

9919

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2611

AN:

3466

East Asian (EAS)

AF:

0.450

AC:

2316

AN:

5142

South Asian (SAS)

AF:

0.461

AC:

2205

AN:

4784

European-Finnish (FIN)

AF:

0.661

AC:

6901

AN:

10444

Middle Eastern (MID)

AF:

0.614

AC:

178

AN:

290

European-Non Finnish (NFE)

AF:

0.646

AC:

43883

AN:

67938

Other (OTH)

AF:

0.653

AC:

1373

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1698

3396

5095

6793

8491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.655

Hom.:

98671

Bravo

AF:

0.675

Asia WGS

AF:

0.468

AC:

1627

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.653

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Citrin deficiency (1)

Citrullinemia (1)

Citrullinemia type I (1)

Citrullinemia type II (1)

Citrullinemia, type II, adult-onset (1)

Neonatal intrahepatic cholestasis due to citrin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

-0.32

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000092

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over