rs78430478

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014251.3(SLC25A13):c.93T>C(p.Gly31Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,018 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

SLC25A13
NM_014251.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.117

Publications

0 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=-0.54).

BP6

Variant 7-96277315-A-G is Benign according to our data. Variant chr7-96277315-A-G is described in ClinVar as Benign. ClinVar VariationId is 260372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.117 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1546/152246) while in subpopulation AFR AF = 0.0357 (1485/41546). AF 95% confidence interval is 0.0342. There are 26 homozygotes in GnomAd4. There are 754 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3 link	c.93T>C	p.Gly31Gly	synonymous_variant	Exon 3 of 18	ENST00000265631.10	NP_055066.1	Q9UJS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A13	ENST00000265631.10 link	c.93T>C	p.Gly31Gly	synonymous_variant	Exon 3 of 18	1	NM_014251.3	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6 link	c.93T>C	p.Gly31Gly	synonymous_variant	Exon 3 of 18	1		ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000472162.2 link	n.93T>C		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000473505.1	R4GN64

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1540

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00255

AC:

637

AN:

249874

AF XY:

0.00184

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00104

AC:

1518

AN:

1460772

Hom.:

Cov.:

AF XY:

0.000877

AC XY:

637

AN XY:

726636

show subpopulations

African (AFR)

AF:

0.0371

AC:

1241

AN:

33432

American (AMR)

AF:

0.00226

AC:

101

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1111506

Other (OTH)

AF:

0.00215

AC:

130

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

138

206

275

344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0102

AC:

1546

AN:

152246

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

754

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0357

AC:

1485

AN:

41546

American (AMR)

AF:

0.00288

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68022

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00422

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00289

AC:

AN:

3474

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Citrin deficiency

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.54

CADD

Benign

7.9

(source)

DANN

Benign

0.72

PhyloP100

-0.12

Mutation Taster

=292/8

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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