NM_014251.3:c.*175A>G

Variant names:

• chr7-96121016-T-C
• rs144877897
• NM_014251.3:c.*175A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014251.3(SLC25A13):​c.*175A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 771,954 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (26 hom.)
• Consequence: SLC25A13 NM_014251.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.38
• 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), 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-96121016-T-C is Benign according to our data. Variant chr7-96121016-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 361008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 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.*175A>G		3_prime_UTR	Exon 18 of 18	NP_055066.1	Q9UJS0-1
	SLC25A13	NM_001160210.2		c.*175A>G		3_prime_UTR	Exon 18 of 18	NP_001153682.1	Q9UJS0-2
	SLC25A13	NR_027662.2		n.2229A>G		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.*175A>G		3_prime_UTR	Exon 18 of 18	ENSP00000265631.6	Q9UJS0-1
	SLC25A13	ENST00000416240.6	TSL:1	c.*175A>G		3_prime_UTR	Exon 18 of 18	ENSP00000400101.2	Q9UJS0-2
	SLC25A13	ENST00000856215.1		c.*175A>G		3_prime_UTR	Exon 19 of 19	ENSP00000526274.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2333 AN: 152172 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00358 AC: 494 AN: 138104 AF XY: 0.00296

Gnomad AFR exome AF: 0.0593

Gnomad AMR exome AF: 0.00300

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00193

GnomAD4 exome AF: 0.00194 AC: 1204 AN: 619664 Hom.: 26 Cov.: 8 AF XY: 0.00160 AC XY: 530 AN XY: 331276

African (AFR) AF: 0.0528 AC: 896 AN: 16984

American (AMR) AF: 0.00326 AC: 113 AN: 34696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20344

East Asian (EAS) AF: 0.00 AC: 0 AN: 32130

South Asian (SAS) AF: 0.000142 AC: 9 AN: 63388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34096

Middle Eastern (MID) AF: 0.00115 AC: 3 AN: 2604

European-Non Finnish (NFE) AF: 0.000138 AC: 53 AN: 382876

Other (OTH) AF: 0.00399 AC: 130 AN: 32546

GnomAD4 genome AF: 0.0154 AC: 2348 AN: 152290 Hom.: 61 Cov.: 33 AF XY: 0.0151 AC XY: 1126 AN XY: 74460

African (AFR) AF: 0.0532 AC: 2211 AN: 41558

American (AMR) AF: 0.00575 AC: 88 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2110

Alfa AF: 0.00759 Hom.: 3

Bravo AF: 0.0164

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Citrullinemia type I (1)
-	-	1	Citrullinemia type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		1.4
Mutation Taster		=100/0	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: rs144877897; hg19: chr7-95750328;