Variant chr22-23958576-G-A 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.326C>T(p.Thr109Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 16)

Exomes 𝑓: 0.00014 ( 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: 0.623

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=0.15803152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTT2B	NM_001080843.4 linkuse as main transcript	c.326C>T	p.Thr109Ile	missense_variant	3/5	ENST00000290765.9
GSTT2B	NM_001363804.1 linkuse as main transcript	c.326C>T	p.Thr109Ile	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTT2B	ENST00000290765.9 linkuse as main transcript	c.326C>T	p.Thr109Ile	missense_variant	3/5	1	NM_001080843.4	P1
GSTT2B	ENST00000404172.3 linkuse as main transcript	c.326C>T	p.Thr109Ile	missense_variant	3/5	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

127238

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000817

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:

0.000155

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000143

AC:

172

AN:

1204464

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

607356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000191

Gnomad4 OTH exome

AF:

0.0000576

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000865

AC:

AN:

127238

Hom.:

Cov.:

AF XY:

0.0000494

AC XY:

AN XY:

60708

show subpopulations

Gnomad4 AFR

AF:

0.0000275

Gnomad4 AMR

AF:

0.0000817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000155

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000148

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

Sep 20, 2023

The c.326C>T (p.T109I) alteration is located in exon 3 (coding exon 3) of the GSTT2 gene. This alteration results from a C to T substitution at nucleotide position 326, causing the threonine (T) at amino acid position 109 to be replaced by an isoleucine (I). 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

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.9

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.10

Sift

Benign

0.095

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.98

D;P

Vest4

0.22

MutPred

0.69

Gain of catalytic residue at L114 (P = 0.1193);Gain of catalytic residue at L114 (P = 0.1193);

MVP

0.093

MPC

2.4

ClinPred

0.068

GERP RS

0.65

Varity_R

0.13

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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