7-96277250-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_014251.3(SLC25A13):c.158C>G(p.Pro53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P53L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A13
NM_014251.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.27

Publications

2 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: 0.30459 (below the threshold of 3.09). Trascript score misZ: 1.1434 (below the threshold of 3.09). GenCC associations: The gene is linked to citrin deficiency, neonatal intrahepatic cholestasis due to citrin deficiency, citrullinemia, type II, adult-onset, citrullinemia type II.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3 link	c.158C>G	p.Pro53Arg	missense_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.158C>G	p.Pro53Arg	missense_variant	Exon 3 of 18	1	NM_014251.3	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6 link	c.158C>G	p.Pro53Arg	missense_variant	Exon 3 of 18	1		ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000472162.2 link	n.158C>G		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000473505.1	R4GN64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247196

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33390

American (AMR)

AF:

0.00

AC:

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110534

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.0060

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

L;L

PhyloP100

4.3

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.23

Sift

Benign

0.33

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

B;.

Vest4

0.63

MutPred

0.35

Loss of glycosylation at P53 (P = 0.0542);Loss of glycosylation at P53 (P = 0.0542);

MVP

0.85

MPC

0.12

ClinPred

0.31

GERP RS

4.4

Varity_R

0.096

gMVP

0.52

Mutation Taster

=59/41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over