chr22-23958621-C-T

Variant names:

• chr22-23958621-C-T
• rs1370190810
• NM_001080843.4:c.281G>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.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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.162
• 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=0.24624434).

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

Sel.	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: 4 AN: 92830 Hom.: 0 Cov.: 12

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: 6 AN: 65246 AF XY: 0.000122

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: 25 AN: 895682 Hom.: 0 Cov.: 13 AF XY: 0.0000151 AC XY: 7 AN XY: 463354

African (AFR) AF: 0.0000784 AC: 2 AN: 25502

American (AMR) AF: 0.000218 AC: 9 AN: 41226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21662

East Asian (EAS) AF: 0.00 AC: 0 AN: 36320

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 0.0000116 AC: 7 AN: 603052

Other (OTH) AF: 0.000144 AC: 6 AN: 41792

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000430 AC: 4 AN: 92924 Hom.: 0 Cov.: 12 AF XY: 0.0000919 AC XY: 4 AN XY: 43522

African (AFR) AF: 0.00 AC: 0 AN: 27906

American (AMR) AF: 0.000358 AC: 3 AN: 8386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2436

East Asian (EAS) AF: 0.00 AC: 0 AN: 2534

South Asian (SAS) AF: 0.00 AC: 0 AN: 1630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.0000232 AC: 1 AN: 43184

Other (OTH) AF: 0.00 AC: 0 AN: 1118

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	Benign	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.017	N
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.16
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.049
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.060	T
Polyphen		0.95	P
Vest4		0.20
MutPred		0.50		Loss of methylation at R94 (P = 0.0148)
MVP		0.068
MPC		2.1
ClinPred		0.25	T
GERP RS		-0.94
Varity_R		0.17
gMVP		0.50
Mutation Taster		=89/11	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: rs1370190810; hg19: chr22-24300808;