Variant chr6-52752940-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000493422.3(GSTA2):c.328C>T(p.Pro110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,613,666 control chromosomes in the GnomAD database, including 2,655 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.039 ( 220 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2435 hom. )

Consequence

GSTA2
ENST00000493422.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

Variant links:

Genes affected

GSTA2 (HGNC:4627): (glutathione S-transferase alpha 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation. [provided by RefSeq, Jul 2008]

GSTA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA2	NM_000846.5 linkuse as main transcript	c.328C>T	p.Pro110Ser	missense_variant	5/7	ENST00000493422.3	NP_000837.3
GSTA2	XM_047418684.1 linkuse as main transcript	c.328C>T	p.Pro110Ser	missense_variant	6/8		XP_047274640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA2	ENST00000493422.3 linkuse as main transcript	c.328C>T	p.Pro110Ser	missense_variant	5/7	1	NM_000846.5	ENSP00000420168	P1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5977

AN:

152096

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00715

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0383

GnomAD3 exomes

AF:

0.0565

AC:

14200

AN:

251234

Hom.:

690

AF XY:

0.0616

AC XY:

8366

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00627

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0384

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0486

AC:

71063

AN:

1461452

Hom.:

2435

Cov.:

AF XY:

0.0508

AC XY:

36952

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.00586

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0228

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0400

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0393

AC:

5977

AN:

152214

Hom.:

220

Cov.:

AF XY:

0.0444

AC XY:

3302

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00713

Gnomad4 AMR

AF:

0.0251

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0389

Hom.:

407

Bravo

AF:

0.0288

TwinsUK

AF:

0.0407

AC:

151

ALSPAC

AF:

0.0402

AC:

155

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.0347

AC:

298

ExAC

AF:

0.0569

AC:

6904

Asia WGS

AF:

0.129

AC:

448

AN:

3478

EpiCase

AF:

0.0357

EpiControl

AF:

0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.016

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.12

Sift

Benign

0.091

Sift4G

Benign

0.11

Polyphen

0.0050

Vest4

0.066

MPC

0.020

ClinPred

0.018

GERP RS

1.3

Varity_R

0.27

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -8

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