Variant 22-23960293-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBS2_Supporting

The NM_001080843.4(GSTT2B):c.200+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,611,566 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00030 ( 9 hom. )

Consequence

GSTT2B
NM_001080843.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.12

Variant links:

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]

GSTT2B links:

ENSG00000290199 (HGNC:):

ENSG00000290199 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 22-23960293-C-T is Pathogenic according to our data. Variant chr22-23960293-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3064991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTT2B	NM_001080843.4 link	c.200+1G>A		splice_donor_variant, intron_variant	Intron 2 of 4	ENST00000290765.9	NP_001074312.1	P0CG30G9J6Q5
GSTT2B	NM_001363804.1 link	c.200+1G>A		splice_donor_variant, intron_variant	Intron 2 of 4		NP_001350733.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSTT2B	ENST00000290765.9 link	c.200+1G>A	splice_donor_variant, intron_variant	Intron 2 of 4	1	NM_001080843.4	ENSP00000290765.4	P0CG30
GSTT2B	ENST00000404172.3 link	c.200+1G>A	splice_donor_variant, intron_variant	Intron 2 of 4	1		ENSP00000385116.3	Q6ICJ4
ENSG00000290199	ENST00000703580.1 link	n.309+13475G>A	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.000370

AC:

AN:

151320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00609

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000281

Gnomad OTH

AF:

0.000482

GnomAD4 exome

AF:

0.000295

AC:

431

AN:

1460138

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

241

AN XY:

726408

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00649

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000534

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.000680

GnomAD4 genome

AF:

0.000376

AC:

AN:

151428

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00609

Gnomad4 EAS

AF:

0.000393

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000281

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.00358

Hom.:

ExAC

AF:

0.00641

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 1

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Mar 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.96

Eigen

Uncertain

0.50

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.71

GERP RS

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.88

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.54

Position offset: 23

DS_DL_spliceai

0.99

Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over