rs150082469

Variant names:

• chr7-96121909-G-A
• rs150082469
• NM_014251.3:c.1680C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-96121909-G-A
• chr7-96121909-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_014251.3(SLC25A13):​c.1680C>T​(p.Ser560Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,064 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (10 hom.)
• Consequence: SLC25A13 NM_014251.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.399
• Publications: 6 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 7-96121909-G-A is Benign according to our data. Variant chr7-96121909-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 290076.
• BP7: Synonymous conserved (PhyloP=-0.399 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 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.1680C>T	p.Ser560Ser	synonymous	Exon 16 of 18	NP_055066.1	Q9UJS0-1
	SLC25A13	NM_001160210.2		c.1683C>T	p.Ser561Ser	synonymous	Exon 16 of 18	NP_001153682.1	Q9UJS0-2
	SLC25A13	NR_027662.2		n.1706C>T		non_coding_transcript_exon	Exon 15 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.1680C>T	p.Ser560Ser	synonymous	Exon 16 of 18	ENSP00000265631.6	Q9UJS0-1
	SLC25A13	ENST00000416240.6	TSL:1	c.1683C>T	p.Ser561Ser	synonymous	Exon 16 of 18	ENSP00000400101.2	Q9UJS0-2
	SLC25A13	ENST00000856215.1		c.1800C>T	p.Ser600Ser	synonymous	Exon 17 of 19	ENSP00000526274.1

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 363 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00453

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00237 AC: 595 AN: 251418 AF XY: 0.00234

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00346 AC: 5053 AN: 1461890 Hom.: 10 Cov.: 31 AF XY: 0.00335 AC XY: 2435 AN XY: 727248

African (AFR) AF: 0.000866 AC: 29 AN: 33480

American (AMR) AF: 0.00157 AC: 70 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.00429 AC: 4770 AN: 1112010

Other (OTH) AF: 0.00219 AC: 132 AN: 60396

GnomAD4 genome AF: 0.00239 AC: 363 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74388

African (AFR) AF: 0.000723 AC: 30 AN: 41514

American (AMR) AF: 0.00111 AC: 17 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00453 AC: 308 AN: 68010

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00326 Hom.: 2

Bravo AF: 0.00247

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00485

EpiControl AF: 0.00498

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Citrin deficiency (1)
-	1	-	Citrullinemia type II (1)
-	-	1	Late-onset citrullinemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.8
DANN	Benign	0.63
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150082469; hg19: chr7-95751221; COSMIC: COSV55712793; COSMIC: COSV55712793;