7-96234796-T-C

Position:

chr7-96234796-T-C

Variant summary

Our verdict is Benign. Variant got -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:9

Conservation

PhyloP100: -0.323

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 Benign. Variant got -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 id is 260371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-96234796-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A13	NM_014251.3 linkuse as main transcript	c.328+6A>G		splice_region_variant, intron_variant		ENST00000265631.10	NP_055066.1	Q9UJS0-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SLC25A13	ENST00000265631.10 linkuse as main transcript	c.328+6A>G	splice_region_variant, intron_variant	1	NM_014251.3	ENSP00000265631.6	Q9UJS0-1
SLC25A13	ENST00000416240.6 linkuse as main transcript	c.328+6A>G	splice_region_variant, intron_variant	1		ENSP00000400101.2	Q9UJS0-2
SLC25A13	ENST00000472162.2 linkuse as main transcript	n.213-25819A>G	intron_variant	4		ENSP00000473505.1	R4GN64

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

GnomAD3 exomes

AF:

0.616

AC:

154731

AN:

251160

Hom.:

48753

AF XY:

0.607

AC XY:

82411

AN XY:

135756

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 SAS exome

AF:

0.464

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

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.628

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.640

Gnomad4 NFE exome

AF:

0.647

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.667

AC:

101251

AN:

151806

Hom.:

34153

Cov.:

AF XY:

0.662

AC XY:

49059

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.650

Gnomad4 ASJ

AF:

0.753

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.653

Alfa

AF:

0.651

Hom.:

64083

Bravo

AF:

0.675

Asia WGS

AF:

0.468

AC:

1627

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.653

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	Allele frequency is common in at least one population database (frequency: 74.812% in gnomAD_Exomes) based on the frequency threshold of 1.504% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. 3 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Neonatal intrahepatic cholestasis due to citrin deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Citrin deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Citrullinemia

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 18, 2019

- -

Citrullinemia type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Citrullinemia, type II, adult-onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Citrullinemia type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.64

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

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