7-96277250-G-C

Position:

• chr7-96277250-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014251.3(SLC25A13):​c.158C>G​(p.Pro53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A13 NM_014251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A13	NM_014251.3	c.158C>G	p.Pro53Arg	missense_variant	3/18	ENST00000265631.10	NP_055066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A13	ENST00000265631.10	c.158C>G	p.Pro53Arg	missense_variant	3/18	1	NM_014251.3	ENSP00000265631.6
SLC25A13	ENST00000416240.6	c.158C>G	p.Pro53Arg	missense_variant	3/18	1		ENSP00000400101.2
SLC25A13	ENST00000472162.2	n.158C>G		non_coding_transcript_exon_variant	3/5	4		ENSP00000473505.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247196 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458866 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.0060
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.23
Sift	Benign	0.33	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0	B;.
Vest4		0.63
MutPred		0.35		Loss of glycosylation at P53 (P = 0.0542);Loss of glycosylation at P53 (P = 0.0542);
MVP		0.85
MPC		0.12
ClinPred		0.31	T
GERP RS		4.4
Varity_R		0.096
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs753950441; hg19: chr7-95906562;