5-141303514-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031947.4(SLC25A2):c.352G>A(p.Ala118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,614,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

SLC25A2
NM_031947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

SLC25A2 (HGNC:22921): (solute carrier family 25 member 2) This intronless gene encodes a protein that localizes to the mitochondrial inner membrane and likely functions as a transporter of small molecules such as ornithine. This gene is located between the protocadherin beta and gamma gene clusters on chromosome 5. [provided by RefSeq, Dec 2014]

SLC25A2 links:

TAF7 (HGNC:11541): (TATA-box binding protein associated factor 7) The intronless gene for this transcription coactivator is located between the protocadherin beta and gamma gene clusters on chromosome 5. The protein encoded by this gene is a component of the TFIID protein complex, a complex which binds to the TATA box in class II promoters and recruits RNA polymerase II and other factors. This particular subunit interacts with the largest TFIID subunit, as well as multiple transcription activators. The protein is required for transcription by promoters targeted by RNA polymerase II. [provided by RefSeq, Jul 2008]

TAF7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.063889384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A2	NM_031947.4 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 1 of 1	ENST00000239451.7	NP_114153.1	Q9BXI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC25A2	ENST00000239451.7 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 1 of 1	6	NM_031947.4	ENSP00000239451.4	Q9BXI2
TAF7	ENST00000624699.1 link	n.128+17004G>A		intron_variant	Intron 1 of 2	3
TAF7	ENST00000686518.1 link	n.75+17004G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251474

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000978

AC:

143

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000890

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000315

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000366

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.352G>A (p.A118T) alteration is located in exon 1 (coding exon 1) of the SLC25A2 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the alanine (A) at amino acid position 118 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.016

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.71

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.29

Polyphen

0.033

Vest4

0.14

MVP

0.83

MPC

0.20

ClinPred

0.013

GERP RS

1.9

Varity_R

0.050

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over