Variant chr22-23960298-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS2_Supporting

The NM_001080843.4(GSTT2B):c.196G>A(p.Glu66Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0019 in 1,612,624 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

GSTT2B
NM_001080843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3751099).

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTT2B	NM_001080843.4 linkuse as main transcript	c.196G>A	p.Glu66Lys	missense_variant	2/5	ENST00000290765.9
GSTT2B	NM_001363804.1 linkuse as main transcript	c.196G>A	p.Glu66Lys	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTT2B	ENST00000290765.9 linkuse as main transcript	c.196G>A	p.Glu66Lys	missense_variant	2/5	1	NM_001080843.4	P1
GSTT2B	ENST00000404172.3 linkuse as main transcript	c.196G>A	p.Glu66Lys	missense_variant	2/5	1

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

235

AN:

151756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00264

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00196

AC:

AN:

39848

Hom.:

AF XY:

0.00204

AC XY:

AN XY:

20128

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00208

Gnomad FIN exome

AF:

0.000427

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00193

AC:

2824

AN:

1460750

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1427

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00217

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

151874

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00264

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000598

Hom.:

ExAC

AF:

0.000212

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.196G>A (p.E66K) alteration is located in exon 2 (coding exon 2) of the GSTT2B gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glutamic acid (E) at amino acid position 66 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.062

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.065

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

4.1

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

0.96

D;D

Vest4

0.77

MutPred

0.92

Gain of methylation at E66 (P = 0.01);Gain of methylation at E66 (P = 0.01);

MVP

0.84

MPC

2.1

ClinPred

0.16

GERP RS

2.4

Varity_R

0.86

gMVP

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over