Genetic Variant GSTT2B:p.Met139Ile (chr22-23958393-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001080843.4(GSTT2B):c.417G>A(p.Met139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,428,374 control chromosomes in the GnomAD database, including 1,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.066 ( 334 hom., cov: 19)

Exomes 𝑓: 0.032 ( 1675 hom. )

Failed GnomAD Quality Control

Consequence

GSTT2B
NM_001080843.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.578

Variant links:

Genes affected

GSTT2B (HGNC:33437): (glutathione S-transferase theta 2B) The protein encoded by this gene, glutathione S-transferase (GST) theta 2B (GSTT2B), is a member of a superfamily of proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. Human GSTs can be divided into five main classes: alpha, mu, pi, theta, and zeta. The theta class includes GSTT1, GSTT2, and GSTT2B. GSTT2 and GSTT2B are nearly identical to each other, and share 55% amino acid identity with GSTT1. All three genes may play a role in human carcinogenesis. The GSTT2B gene is a pseudogene in some populations. [provided by RefSeq, Sep 2015]

GSTT2B links:

ENSG00000290199 (HGNC:):

ENSG00000290199 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=0.004102975).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTT2B	NM_001080843.4 link	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5	ENST00000290765.9	NP_001074312.1	P0CG30G9J6Q5
GSTT2B	NM_001363804.1 link	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5		NP_001350733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSTT2B	ENST00000290765.9 link	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5	1	NM_001080843.4	ENSP00000290765.4	P0CG30
GSTT2B	ENST00000404172.3 link	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5	1		ENSP00000385116.3	Q6ICJ4
ENSG00000290199	ENST00000703580.1 link	n.309+15375G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0661

AC:

9882

AN:

149544

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0268

Gnomad AMR

AF:

0.0595

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0604

Gnomad FIN

AF:

0.00514

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0563

GnomAD3 exomes

AF:

0.0530

AC:

12869

AN:

242684

Hom.:

746

AF XY:

0.0486

AC XY:

6380

AN XY:

131396

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0828

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.0533

Gnomad FIN exome

AF:

0.00543

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0316

AC:

45122

AN:

1428374

Hom.:

1675

Cov.:

AF XY:

0.0316

AC XY:

22497

AN XY:

711414

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0781

Gnomad4 ASJ exome

AF:

0.0350

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.00601

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0485

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0662

AC:

9906

AN:

149656

Hom.:

334

Cov.:

AF XY:

0.0661

AC XY:

4830

AN XY:

73024

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.0596

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.0607

Gnomad4 FIN

AF:

0.00514

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0318

Hom.:

ESP6500AA

AF:

0.140

AC:

615

ESP6500EA

AF:

0.0193

AC:

166

ExAC

AF:

0.0540

AC:

6552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

DANN

Benign

0.82

DEOGEN2

Benign

0.0050

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.94

L;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.048

Sift

Benign

0.18

T;T

Sift4G

Benign

0.069

T;T

Polyphen

0.0

B;B

Vest4

0.079

MutPred

0.56

Loss of disorder (P = 0.0838);Loss of disorder (P = 0.0838);

MPC

1.9

ClinPred

0.0021

GERP RS

-0.12

Varity_R

0.090

gMVP

0.42

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