Genetic Variant NM_031947.4:c.542T>G (chr5-141303324-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031947.4(SLC25A2):c.542T>G(p.Val181Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,614,202 control chromosomes in the GnomAD database, including 1,153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.017 ( 137 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1016 hom. )

Consequence

SLC25A2
NM_031947.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.77

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024497807).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A2	NM_031947.4 link	c.542T>G	p.Val181Gly	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.542T>G	p.Val181Gly	missense_variant	Exon 1 of 1	6	NM_031947.4	ENSP00000239451.4	Q9BXI2
TAF7	ENST00000624699.1 link	n.128+17194T>G		intron_variant	Intron 1 of 2	3
TAF7	ENST00000686518.1 link	n.75+17194T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2617

AN:

152202

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0378

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0382

AC:

9604

AN:

251392

Hom.:

735

AF XY:

0.0331

AC XY:

4500

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.0952

Gnomad SAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0118

AC:

17310

AN:

1461882

Hom.:

1016

Cov.:

AF XY:

0.0119

AC XY:

8681

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0944

Gnomad4 SAS exome

AF:

0.0378

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0173

AC:

2634

AN:

152320

Hom.:

137

Cov.:

AF XY:

0.0200

AC XY:

1489

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.0379

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.00173

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00805

Hom.:

144

Bravo

AF:

0.0258

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.0319

AC:

3878

Asia WGS

AF:

0.0650

AC:

224

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.87

Vest4

0.18

MPC

0.82

ClinPred

0.047

GERP RS

3.8

Varity_R

0.78

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over