rs35539807

Variant names:

• chr7-96121335-G-A
• rs35539807
• NM_014251.3:c.1884C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-96121335-G-A
• chr7-96121335-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014251.3(SLC25A13):​c.1884C>T​(p.Asn628Asn) 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:7
• Conservation: PhyloP100: -0.518
• Publications: 1 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=-0.83).
• BP6: Variant 7-96121335-G-A is Benign according to our data. Variant chr7-96121335-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 361011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1884C>T	p.Asn628Asn	synonymous	Exon 18 of 18	NP_055066.1	Q9UJS0-1
	SLC25A13	NM_001160210.2		c.1887C>T	p.Asn629Asn	synonymous	Exon 18 of 18	NP_001153682.1	Q9UJS0-2
	SLC25A13	NR_027662.2		n.1910C>T		non_coding_transcript_exon	Exon 17 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A13	ENST00000265631.10	TSL:1 MANE Select	c.1884C>T	p.Asn628Asn	synonymous	Exon 18 of 18	ENSP00000265631.6	Q9UJS0-1
	SLC25A13	ENST00000416240.6	TSL:1	c.1887C>T	p.Asn629Asn	synonymous	Exon 18 of 18	ENSP00000400101.2	Q9UJS0-2
	SLC25A13	ENST00000856215.1		c.2004C>T	p.Asn668Asn	synonymous	Exon 19 of 19	ENSP00000526274.1

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

GnomAD2 exomes AF: 0.00667 AC: 1677 AN: 251406 AF XY: 0.00495

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 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

African (AFR) AF: 0.0881 AC: 2949 AN: 33478

American (AMR) AF: 0.00505 AC: 226 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5768

European-Non Finnish (NFE) AF: 0.000302 AC: 336 AN: 1112000

Other (OTH) AF: 0.00584 AC: 353 AN: 60396

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

African (AFR) AF: 0.0835 AC: 3466 AN: 41530

American (AMR) AF: 0.00947 AC: 145 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68020

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0112 Hom.: 35

Bravo AF: 0.0280

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Citrin deficiency (1)
-	-	1	Citrullinemia type I (1)
-	-	1	Citrullinemia type II (1)
-	-	1	Late-onset citrullinemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs35539807; hg19: chr7-95750647;