Variant chr7-96321955-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

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 Uncertain significance (★).

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

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 links:

SLC25A13 (HGNC:):

SLC25A13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A13	NM_014251.3 linkuse as main transcript	c.2T>A	p.Met1?	start_lost	1/18	ENST00000265631.10	NP_055066.1	Q9UJS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC25A13	ENST00000265631.10 linkuse as main transcript	c.2T>A	p.Met1?	start_lost	1/18	1	NM_014251.3	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6 linkuse as main transcript	c.2T>A	p.Met1?	start_lost	1/18	1		ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000472162.2 linkuse as main transcript	n.2T>A		non_coding_transcript_exon_variant	1/5	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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jun 17, 2024

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

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

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

Varity_R

0.88

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over