chr22-23958409-C-T

Variant names:

• chr22-23958409-C-T
• rs143373337
• NM_001080843.4:c.401G>A

Variant summary

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

The NM_001080843.4(GSTT2B):​c.401G>A​(p.Arg134His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,459,986 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00012 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00025 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.05
• Publications: 2 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=0.03497815).

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.401G>A	p.Arg134His	missense	Exon 4 of 5	NP_001074312.1	P0CG30
	GSTT2B	NM_001363804.1		c.401G>A	p.Arg134His	missense	Exon 4 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.401G>A	p.Arg134His	missense	Exon 4 of 5	ENSP00000290765.4	P0CG30
	GSTT2B	ENST00000404172.3	TSL:1	c.401G>A	p.Arg134His	missense	Exon 4 of 5	ENSP00000385116.3	Q6ICJ4
	GSTT2B	ENST00000895419.1		c.503G>A	p.Arg168His	missense	Exon 5 of 6	ENSP00000565478.1

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151716 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000145

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: 0.000380

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000139 AC: 34 AN: 244704 AF XY: 0.000166

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000684

Gnomad NFE exome AF: 0.000145

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000248 AC: 362 AN: 1459986 Hom.: 1 Cov.: 30 AF XY: 0.000229 AC XY: 166 AN XY: 726222

African (AFR) AF: 0.0000896 AC: 3 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85982

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000294 AC: 326 AN: 1110726

Other (OTH) AF: 0.000116 AC: 7 AN: 60304

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000119 AC: 18 AN: 151834 Hom.: 0 Cov.: 19 AF XY: 0.0000944 AC XY: 7 AN XY: 74168

African (AFR) AF: 0.000145 AC: 6 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.000380 AC: 4 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67888

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

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	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.1
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.042
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.60	P
Vest4		0.15
MVP		0.13
MPC		2.4
ClinPred		0.22	T
GERP RS		-0.13
Varity_R		0.10
gMVP		0.40
Mutation Taster		=87/13	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: rs143373337; hg19: chr22-24300596; COSMIC: COSV51960027; COSMIC: COSV51960027;