22-23958344-A-C

Variant names:

• chr22-23958344-A-C
• NM_001080843.4:c.466T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001080843.4(GSTT2B):​c.466T>G​(p.Phe156Val) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 8.0e-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: 7.41

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTT2B	NM_001080843.4	c.466T>G	p.Phe156Val	missense_variant	Exon 4 of 5	ENST00000290765.9	NP_001074312.1
GSTT2B	NM_001363804.1	c.466T>G	p.Phe156Val	missense_variant	Exon 4 of 5		NP_001350733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTT2B	ENST00000290765.9	c.466T>G	p.Phe156Val	missense_variant	Exon 4 of 5	1	NM_001080843.4	ENSP00000290765.4
GSTT2B	ENST00000404172.3	c.466T>G	p.Phe156Val	missense_variant	Exon 4 of 5	1		ENSP00000385116.3
ENSG00000290199	ENST00000703580.1	n.309+15424T>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.97e-7 AC: 1 AN: 1255420 Hom.: 0 Cov.: 20 AF XY: 0.00000159 AC XY: 1 AN XY: 630854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466T>G (p.F156V) alteration is located in exon 4 (coding exon 4) of the GSTT2B gene. This alteration results from a T to G substitution at nucleotide position 466, causing the phenylalanine (F) at amino acid position 156 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.9	H;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.74		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.52
MPC		3.7
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.90
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24300531;