Variant chr6-52982633-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001512.4(GSTA4):c.487A>G(p.Thr163Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,610,380 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

GSTA4
NM_001512.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

GSTA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007360488).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GSTA4	NM_001512.4 linkuse as main transcript	c.487A>G	p.Thr163Ala	missense_variant	6/7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5 linkuse as main transcript	c.487A>G	p.Thr163Ala	missense_variant	6/7		XP_005249092.1
GSTA4	XM_011514534.4 linkuse as main transcript	c.376A>G	p.Thr126Ala	missense_variant	5/6		XP_011512836.1
GSTA4	XM_011514535.4 linkuse as main transcript	c.376A>G	p.Thr126Ala	missense_variant	5/6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9 linkuse as main transcript	c.487A>G	p.Thr163Ala	missense_variant	6/7	1	NM_001512.4	ENSP00000360002	P1	O15217-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251108

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1458096

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

161

AN XY:

725642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00820

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000177

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00462

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000518

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.064

T;.;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

.;T;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0074

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.35

N;.;N;.

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

1.1

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.81

T;T;T;T

Sift4G

Benign

0.94

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.083

MVP

0.17

MPC

0.12

ClinPred

0.045

GERP RS

4.1

Varity_R

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over