22-23958576-G-A

Variant names:

• chr22-23958576-G-A
• rs761523379
• NM_001080843.4:c.326C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.623
• 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=0.15803152).

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.326C>T	p.Thr109Ile	missense	Exon 3 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.326C>T	p.Thr109Ile	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.326C>T	p.Thr109Ile	missense	Exon 3 of 5	ENSP00000290765.4	P0CG30
	GSTT2B	ENST00000404172.3	TSL:1	c.326C>T	p.Thr109Ile	missense	Exon 3 of 5	ENSP00000385116.3	Q6ICJ4
	GSTT2B	ENST00000895419.1		c.428C>T	p.Thr143Ile	missense	Exon 4 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes AF: 0.0000865 AC: 11 AN: 127238 Hom.: 0 Cov.: 16

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

GnomAD2 exomes AF: 0.0000958 AC: 7 AN: 73036 AF XY: 0.000135

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: 0.000211

Gnomad OTH exome AF: 0.000439

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000143 AC: 172 AN: 1204464 Hom.: 0 Cov.: 18 AF XY: 0.000133 AC XY: 81 AN XY: 607356

⚠️ 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: 30628

American (AMR) AF: 0.00 AC: 0 AN: 41894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23224

East Asian (EAS) AF: 0.00 AC: 0 AN: 38524

South Asian (SAS) AF: 0.00 AC: 0 AN: 76052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5158

European-Non Finnish (NFE) AF: 0.000191 AC: 169 AN: 884642

Other (OTH) AF: 0.0000576 AC: 3 AN: 52040

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000865 AC: 11 AN: 127238 Hom.: 0 Cov.: 16 AF XY: 0.0000494 AC XY: 3 AN XY: 60708

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

African (AFR) AF: 0.0000275 AC: 1 AN: 36384

American (AMR) AF: 0.0000817 AC: 1 AN: 12246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3050

East Asian (EAS) AF: 0.00 AC: 0 AN: 3832

South Asian (SAS) AF: 0.00 AC: 0 AN: 3112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000155 AC: 9 AN: 58128

Other (OTH) AF: 0.00 AC: 0 AN: 1664

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000283328), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000148 AC: 1

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	-0.44	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.9
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.62
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.10
Sift	Benign	0.095	T
Sift4G	Benign	0.25	T
Polyphen		0.98	D
Vest4		0.22
MutPred		0.69		Gain of catalytic residue at L114 (P = 0.1193)
MVP		0.093
MPC		2.4
ClinPred		0.068	T
GERP RS		0.65
Varity_R		0.13
gMVP		0.46
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs761523379; hg19: chr22-24300763;