22-23958564-G-A

Variant names:

• chr22-23958564-G-A
• rs751153388
• NM_001080843.4:c.338C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080843.4(GSTT2B):​c.338C>T​(p.Pro113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00013 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0200
• Publications: 0 publications found

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]

ENSG00000290199 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020792335).

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.338C>T	p.Pro113Leu	missense	Exon 3 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.338C>T	p.Pro113Leu	missense	Exon 3 of 5	NP_001350733.1	Q6ICJ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTT2B	ENST00000290765.9	TSL:1 MANE Select	c.338C>T	p.Pro113Leu	missense	Exon 3 of 5	ENSP00000290765.4	P0CG30
	GSTT2B	ENST00000404172.3	TSL:1	c.338C>T	p.Pro113Leu	missense	Exon 3 of 5	ENSP00000385116.3	Q6ICJ4
	GSTT2B	ENST00000895419.1		c.440C>T	p.Pro147Leu	missense	Exon 4 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes AF: 0.0000362 AC: 5 AN: 138014 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00133

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000219 AC: 16 AN: 72990 AF XY: 0.000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000128 AC: 150 AN: 1174122 Hom.: 2 Cov.: 18 AF XY: 0.000189 AC XY: 112 AN XY: 592176

African (AFR) AF: 0.0000337 AC: 1 AN: 29660

American (AMR) AF: 0.00 AC: 0 AN: 37266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21974

East Asian (EAS) AF: 0.00 AC: 0 AN: 38460

South Asian (SAS) AF: 0.00180 AC: 130 AN: 72142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5072

European-Non Finnish (NFE) AF: 0.00000461 AC: 4 AN: 866858

Other (OTH) AF: 0.000295 AC: 15 AN: 50910

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000362 AC: 5 AN: 138102 Hom.: 0 Cov.: 17 AF XY: 0.0000452 AC XY: 3 AN XY: 66408

African (AFR) AF: 0.00 AC: 0 AN: 38854

American (AMR) AF: 0.00 AC: 0 AN: 13522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3206

East Asian (EAS) AF: 0.00 AC: 0 AN: 4332

South Asian (SAS) AF: 0.00134 AC: 5 AN: 3742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62382

Other (OTH) AF: 0.00 AC: 0 AN: 1838

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000547 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.19
DANN	Benign	0.86
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.77	N
PhyloP100		-0.020
PrimateAI	Benign	0.46	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.050
Sift	Benign	0.36	T
Sift4G	Benign	0.66	T
Polyphen		0.0020	B
Vest4		0.067
MutPred		0.57		Gain of catalytic residue at P113 (P = 0.0056)
MVP		0.043
MPC		1.8
ClinPred		0.024	T
GERP RS		-1.5
Varity_R		0.11
gMVP		0.32
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751153388; hg19: chr22-24300751;