chr6-52896870-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000847.5(GSTA3):c.605G>C(p.Ser202Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00155 in 1,614,050 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 36 hom. )

Consequence

GSTA3
NM_000847.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.86

Publications

7 publications found

Variant links:

Genes affected

GSTA3 (HGNC:4628): (glutathione S-transferase alpha 3) 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 genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

GSTA3 links:

ENSG00000309866 (HGNC:):

ENSG00000309866 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004918754).

BP6

Variant 6-52896870-C-G is Benign according to our data. Variant chr6-52896870-C-G is described in ClinVar as Benign. ClinVar VariationId is 728744.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00159 (2331/1461732) while in subpopulation SAS AF = 0.0192 (1655/86198). AF 95% confidence interval is 0.0184. There are 36 homozygotes in GnomAdExome4. There are 1605 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000847.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA3	NM_000847.5	MANE Select	c.605G>C	p.Ser202Thr	missense	Exon 7 of 7	NP_000838.3
	GSTA3	NM_001363542.2		c.455G>C	p.Ser152Thr	missense	Exon 6 of 6	NP_001350471.1	Q5JW85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTA3	ENST00000211122.4	TSL:1 MANE Select	c.605G>C	p.Ser202Thr	missense	Exon 7 of 7	ENSP00000211122.3	Q16772
GSTA3	ENST00000370968.5	TSL:1	c.455G>C	p.Ser152Thr	missense	Exon 6 of 6	ENSP00000360007.1	Q5JW85
GSTA3	ENST00000961739.1		c.605G>C	p.Ser202Thr	missense	Exon 7 of 7	ENSP00000631798.1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00324

AC:

814

AN:

251394

AF XY:

0.00419

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00159

AC:

2331

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1605

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00221

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00566

AC:

148

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0192

AC:

1655

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000260

AC:

289

AN:

1111936

Other (OTH)

AF:

0.00179

AC:

108

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

102

205

307

410

512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152318

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41566

American (AMR)

AF:

0.00229

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0164

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68036

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000827

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00356

AC:

432

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.0

PhyloP100

5.9

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.19

Sift

Uncertain

0.026

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.32

MVP

0.32

MPC

0.037

ClinPred

0.12

GERP RS

3.3

Varity_R

0.69

gMVP

0.22

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over