rs566389135

Variant names:

• chr22-23958583-G-A
• rs566389135
• NM_001080843.4:c.319C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001080843.4(GSTT2B):​c.319C>T​(p.Arg107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.319C>T	p.Arg107Cys	missense	Exon 3 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.319C>T	p.Arg107Cys	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.319C>T	p.Arg107Cys	missense	Exon 3 of 5	ENSP00000290765.4	P0CG30
	GSTT2B	ENST00000404172.3	TSL:1	c.319C>T	p.Arg107Cys	missense	Exon 3 of 5	ENSP00000385116.3	Q6ICJ4
	GSTT2B	ENST00000895419.1		c.421C>T	p.Arg141Cys	missense	Exon 4 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes AF: 0.0000440 AC: 5 AN: 113536 Hom.: 0 Cov.: 15

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000951

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000704 AC: 5 AN: 71040 AF XY: 0.0000834

Gnomad AFR exome AF: 0.000332

Gnomad AMR exome AF: 0.0000726

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000729

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 31 AN: 1180628 Hom.: 0 Cov.: 18 AF XY: 0.0000268 AC XY: 16 AN XY: 596748

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

African (AFR) AF: 0.0000988 AC: 3 AN: 30376

American (AMR) AF: 0.0000235 AC: 1 AN: 42522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23288

East Asian (EAS) AF: 0.00 AC: 0 AN: 38350

South Asian (SAS) AF: 0.00 AC: 0 AN: 76226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5094

European-Non Finnish (NFE) AF: 0.0000314 AC: 27 AN: 861196

Other (OTH) AF: 0.00 AC: 0 AN: 51270

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000658367), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000440 AC: 5 AN: 113536 Hom.: 0 Cov.: 15 AF XY: 0.0000557 AC XY: 3 AN XY: 53812

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

African (AFR) AF: 0.00 AC: 0 AN: 33166

American (AMR) AF: 0.00 AC: 0 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2834

East Asian (EAS) AF: 0.00 AC: 0 AN: 3204

South Asian (SAS) AF: 0.00 AC: 0 AN: 2394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000951 AC: 5 AN: 52560

Other (OTH) AF: 0.00 AC: 0 AN: 1412

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.043
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.027	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.69		Loss of helix (P = 0.1299)
MVP		0.23
MPC		4.1
ClinPred		0.96	D
GERP RS		1.9
Varity_R		0.77
gMVP		0.72
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

dbSNP: rs566389135; hg19: chr22-24300770;