Genetic Variant NM_001080843.4:c.281G>A (chr22-23958621-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24624434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080843.4. 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
	GSTT2B	NM_001080843.4	MANE Select	c.281G>A	p.Arg94His	missense	Exon 3 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.281G>A	p.Arg94His	missense	Exon 3 of 5	NP_001350733.1	Q6ICJ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTT2B	ENST00000290765.9	TSL:1 MANE Select	c.281G>A	p.Arg94His	missense	Exon 3 of 5	ENSP00000290765.4	P0CG30
GSTT2B	ENST00000404172.3	TSL:1	c.281G>A	p.Arg94His	missense	Exon 3 of 5	ENSP00000385116.3	Q6ICJ4
GSTT2B	ENST00000895419.1		c.383G>A	p.Arg128His	missense	Exon 4 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes

AF:

0.0000431

AC:

AN:

92830

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000920

AC:

AN:

65246

AF XY:

0.000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

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

African (AFR)

AF:

0.0000784

AC:

AN:

25502

American (AMR)

AF:

0.000218

AC:

AN:

41226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21662

East Asian (EAS)

AF:

0.00

AC:

AN:

36320

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4240

European-Non Finnish (NFE)

AF:

0.0000116

AC:

AN:

603052

Other (OTH)

AF:

0.000144

AC:

AN:

41792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

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

African (AFR)

AF:

0.00

AC:

AN:

27906

American (AMR)

AF:

0.000358

AC:

AN:

8386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2436

East Asian (EAS)

AF:

0.00

AC:

AN:

2534

South Asian (SAS)

AF:

0.00

AC:

AN:

1630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.0000232

AC:

AN:

43184

Other (OTH)

AF:

0.00

AC:

AN:

1118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.017

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.0066

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

PhyloP100

0.16

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.049

Sift

Uncertain

0.017

Sift4G

Uncertain

0.060

Polyphen

0.95

Vest4

0.20

MutPred

0.50

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

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over