Variant 22-23958621-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080843.4(GSTT2B):c.281G>A(p.Arg94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GSTT2B
NM_001080843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.162

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:

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=0.24624434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTT2B	NM_001080843.4 link	c.281G>A	p.Arg94His	missense_variant	Exon 3 of 5	ENST00000290765.9	NP_001074312.1	P0CG30G9J6Q5
GSTT2B	NM_001363804.1 link	c.281G>A	p.Arg94His	missense_variant	Exon 3 of 5		NP_001350733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSTT2B	ENST00000290765.9 link	c.281G>A	p.Arg94His	missense_variant	Exon 3 of 5	1	NM_001080843.4	ENSP00000290765.4	P0CG30
GSTT2B	ENST00000404172.3 link	c.281G>A	p.Arg94His	missense_variant	Exon 3 of 5	1		ENSP00000385116.3	Q6ICJ4
ENSG00000290199	ENST00000703580.1 link	n.309+15147G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

92830

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000358

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000232

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000279

AC:

AN:

895682

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

463354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000784

Gnomad4 AMR exome

AF:

0.000218

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000116

Gnomad4 OTH exome

AF:

0.000144

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000430

AC:

AN:

92924

Hom.:

Cov.:

AF XY:

0.0000919

AC XY:

AN XY:

43522

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000358

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000232

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.281G>A (p.R94H) alteration is located in exon 3 (coding exon 3) of the GSTT2 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a histidine (H). 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

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.017

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.049

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.060

T;D

Polyphen

0.95

P;P

Vest4

0.20

MutPred

0.50

Loss of methylation at R94 (P = 0.0148);Loss of methylation at R94 (P = 0.0148);

MVP

0.068

MPC

2.1

ClinPred

0.25

GERP RS

-0.94

Varity_R

0.17

gMVP

0.50

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