7-96121335-G-T

Position:

• chr7-96121335-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014251.3(SLC25A13):​c.1884C>A​(p.Asn628Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N628N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A13 NM_014251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066770434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A13	NM_014251.3	c.1884C>A	p.Asn628Lys	missense_variant	18/18	ENST00000265631.10	NP_055066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A13	ENST00000265631.10	c.1884C>A	p.Asn628Lys	missense_variant	18/18	1	NM_014251.3	ENSP00000265631.6
SLC25A13	ENST00000416240.6	c.1887C>A	p.Asn629Lys	missense_variant	18/18	1		ENSP00000400101.2
SLC25A13	ENST00000494085.1	n.387C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.14
Sift	Benign	0.12	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	B;.
Vest4		0.049
MutPred		0.32		Gain of ubiquitination at N628 (P = 0.0155);.;
MVP		0.52
MPC		0.13
ClinPred		0.041	T
GERP RS		-7.1
Varity_R		0.12
gMVP		0.18

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: rs35539807; hg19: chr7-95750647;