chr7-96321955-A-T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_014251.3(SLC25A13):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC25A13
NM_014251.3 start_lost

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1

Conservation

PhyloP100: 2.23

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)
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: Pathogenic. The variant received 11 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 11 pathogenic variants. Next in-frame start position is after 35 codons. Genomic position: 96277305. Lost 0.051 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-96321955-A-T is Pathogenic according to our data. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931. Variant chr7-96321955-A-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 593931.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A13	NM_014251.3 link	c.2T>A	p.Met1?	start_lost	Exon 1 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.2T>A	p.Met1?	start_lost	Exon 1 of 18	1	NM_014251.3	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6 link	c.2T>A	p.Met1?	start_lost	Exon 1 of 18	1		ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000472162.2 link	n.2T>A		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000473505.1	R4GN64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685954

African (AFR)

AF:

0.00

AC:

AN:

29064

American (AMR)

AF:

0.00

AC:

AN:

35870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24562

East Asian (EAS)

AF:

0.00

AC:

AN:

34174

South Asian (SAS)

AF:

0.00

AC:

AN:

77830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077862

Other (OTH)

AF:

0.00

AC:

AN:

57578

GnomAD4 genome

Cov.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Neonatal intrahepatic cholestasis due to citrin deficiency;CN295299:Citrullinemia, type II, adult-onset

Pathogenic:1

Jun 17, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Sep 07, 2017

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.071

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Uncertain

-0.056

PhyloP100

2.2

PROVEAN

Benign

0.38

N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.46

P;.

Vest4

0.92

MutPred

0.55

Gain of MoRF binding (P = 0.0147);Gain of MoRF binding (P = 0.0147);

MVP

0.94

ClinPred

0.95

GERP RS

4.0

PromoterAI

-0.51

Under-expression

(source)

Varity_R

0.88

gMVP

0.74

Mutation Taster

=9/191

disease causing

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over