rs35539807

chr7-96121335-G-Achr7-96121335-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014251.3(SLC25A13):c.1884C>T(p.Asn628=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,614,162 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (152 hom.)
• Consequence: SLC25A13 NM_014251.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.518

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-96121335-G-A is Benign according to our data. Variant chr7-96121335-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 361011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-96121335-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.518 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A13	NM_014251.3	c.1884C>T	p.Asn628=	synonymous_variant	18/18	ENST00000265631.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A13	ENST00000265631.10	c.1884C>T	p.Asn628=	synonymous_variant	18/18	1	NM_014251.3	A1
SLC25A13	ENST00000416240.6	c.1887C>T	p.Asn629=	synonymous_variant	18/18	1		P5
SLC25A13	ENST00000494085.1	n.387C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3688 AN: 152168 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00667 AC: 1677 AN: 251406 Hom.: 70 AF XY: 0.00495 AC XY: 672 AN XY: 135880

Gnomad AFR exome AF: 0.0884

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000405

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00269 AC: 3938 AN: 1461876 Hom.: 152 Cov.: 31 AF XY: 0.00237 AC XY: 1725 AN XY: 727238

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.00505

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000302

Gnomad4 OTH exome AF: 0.00584

GnomAD4 genome AF: 0.0243 AC: 3698 AN: 152286 Hom.: 146 Cov.: 32 AF XY: 0.0238 AC XY: 1776 AN XY: 74470

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.00947

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0115 Hom.: 28

Bravo AF: 0.0280

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Dec 17, 2020	- -

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. -

Citrin deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Late-onset citrullinemia Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Citrullinemia type I Benign:1

Likely 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	-0.83
Cadd	Benign	1.7
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs35539807; hg19: chr7-95750647;