chr7-96191188-C-T

Variant names:

• chr7-96191188-C-T
• rs78247004
• NM_014251.3:c.675G>A

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.675G>A​(p.Ser225Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,758 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S225S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0094 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: SLC25A13 NM_014251.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.88
• Publications: 2 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), PanelApp Australia
• neonatal intrahepatic cholestasis due to citrin deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet
• citrullinemia type II

  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=-0.67).
• BP6: Variant 7-96191188-C-T is Benign according to our data. Variant chr7-96191188-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 361025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00943 (1433/152020) while in subpopulation AFR AF = 0.0332 (1377/41466). AF 95% confidence interval is 0.0317. There are 25 homozygotes in GnomAd4. There are 650 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	NM_014251.3	MANE Select	c.675G>A	p.Ser225Ser	synonymous	Exon 7 of 18	NP_055066.1	Q9UJS0-1
	SLC25A13	NM_001160210.2		c.675G>A	p.Ser225Ser	synonymous	Exon 7 of 18	NP_001153682.1	Q9UJS0-2
	SLC25A13	NR_027662.2		n.701G>A		non_coding_transcript_exon	Exon 6 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.675G>A	p.Ser225Ser	synonymous	Exon 7 of 18	ENSP00000265631.6	Q9UJS0-1
	SLC25A13	ENST00000416240.6	TSL:1	c.675G>A	p.Ser225Ser	synonymous	Exon 7 of 18	ENSP00000400101.2	Q9UJS0-2
	SLC25A13	ENST00000856215.1		c.675G>A	p.Ser225Ser	synonymous	Exon 7 of 19	ENSP00000526274.1

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1432 AN: 151902 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00265 AC: 665 AN: 251144 AF XY: 0.00194

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00102 AC: 1497 AN: 1461738 Hom.: 16 Cov.: 31 AF XY: 0.000865 AC XY: 629 AN XY: 727176

African (AFR) AF: 0.0344 AC: 1150 AN: 33472

American (AMR) AF: 0.00195 AC: 87 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000764 AC: 85 AN: 1111934

Other (OTH) AF: 0.00263 AC: 159 AN: 60382

GnomAD4 genome AF: 0.00943 AC: 1433 AN: 152020 Hom.: 25 Cov.: 32 AF XY: 0.00875 AC XY: 650 AN XY: 74292

African (AFR) AF: 0.0332 AC: 1377 AN: 41466

American (AMR) AF: 0.00177 AC: 27 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67996

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00421 Hom.: 3

Bravo AF: 0.0105

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Citrin deficiency (1)
-	-	1	Citrullinemia (1)
-	-	1	Citrullinemia type I (1)
-	-	1	Citrullinemia type II (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		-2.9
Mutation Taster		=99/1	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: rs78247004; hg19: chr7-95820500;