7-96277315-A-G

Variant names:

• chr7-96277315-A-G
• rs78430478
• NM_014251.3:c.93T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014251.3(SLC25A13):​c.93T>C​(p.Gly31Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,018 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (20 hom.)
• Consequence: SLC25A13 NM_014251.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.117
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 7-96277315-A-G is Benign according to our data. Variant chr7-96277315-A-G is described in ClinVar as Benign. ClinVar VariationId is 260372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.117 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1546/152246) while in subpopulation AFR AF = 0.0357 (1485/41546). AF 95% confidence interval is 0.0342. There are 26 homozygotes in GnomAd4. There are 754 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014251.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	NM_014251.3	MANE Select	c.93T>C	p.Gly31Gly	synonymous	Exon 3 of 18	NP_055066.1
	SLC25A13	NM_001160210.2		c.93T>C	p.Gly31Gly	synonymous	Exon 3 of 18	NP_001153682.1
	SLC25A13	NR_027662.2		n.235T>C		non_coding_transcript_exon	Exon 3 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.93T>C	p.Gly31Gly	synonymous	Exon 3 of 18	ENSP00000265631.6
	SLC25A13	ENST00000416240.6	TSL:1	c.93T>C	p.Gly31Gly	synonymous	Exon 3 of 18	ENSP00000400101.2
	SLC25A13	ENST00000472162.2	TSL:4	n.93T>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000473505.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1540 AN: 152128 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00255 AC: 637 AN: 249874 AF XY: 0.00184

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00104 AC: 1518 AN: 1460772 Hom.: 20 Cov.: 30 AF XY: 0.000877 AC XY: 637 AN XY: 726636

African (AFR) AF: 0.0371 AC: 1241 AN: 33432

American (AMR) AF: 0.00226 AC: 101 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000929 AC: 8 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5748

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111506

Other (OTH) AF: 0.00215 AC: 130 AN: 60332

GnomAD4 genome AF: 0.0102 AC: 1546 AN: 152246 Hom.: 26 Cov.: 32 AF XY: 0.0101 AC XY: 754 AN XY: 74436

African (AFR) AF: 0.0357 AC: 1485 AN: 41546

American (AMR) AF: 0.00288 AC: 44 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00422 Hom.: 10

Bravo AF: 0.0114

Asia WGS AF: 0.00289 AC: 10 AN: 3474

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Oct 28, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Citrin deficiency Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		-0.12
Mutation Taster		=292/8	polymorphism

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

Other links and lift over

dbSNP: rs78430478; hg19: chr7-95906627;