chr22-23958571-C-T

Variant names:

• chr22-23958571-C-T
• NM_001080843.4:c.331G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080843.4(GSTT2B):​c.331G>A​(p.Gly111Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077147216).

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.331G>A	p.Gly111Ser	missense	Exon 3 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.331G>A	p.Gly111Ser	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.331G>A	p.Gly111Ser	missense	Exon 3 of 5	ENSP00000290765.4	P0CG30
	GSTT2B	ENST00000404172.3	TSL:1	c.331G>A	p.Gly111Ser	missense	Exon 3 of 5	ENSP00000385116.3	Q6ICJ4
	GSTT2B	ENST00000895419.1		c.433G>A	p.Gly145Ser	missense	Exon 4 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.33e-7 AC: 1 AN: 1200490 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 605068

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30480

American (AMR) AF: 0.0000242 AC: 1 AN: 41304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22938

East Asian (EAS) AF: 0.00 AC: 0 AN: 38510

South Asian (SAS) AF: 0.00 AC: 0 AN: 75312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 882724

Other (OTH) AF: 0.00 AC: 0 AN: 51896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 16

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	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.7
DANN	Benign	0.91
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.88	L
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.062	B
Vest4		0.25
MutPred		0.50		Loss of helix (P = 0.2022)
MVP		0.23
MPC		3.2
ClinPred		0.59	D
GERP RS		2.9
Varity_R		0.16
gMVP		0.41
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr22-24300758;