Variant 3-120002133-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001146156.2(GSK3B):c.195A>T(p.Gly65Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,612,362 control chromosomes in the GnomAD database, including 1,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 888 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 820 hom. )

Consequence

GSK3B
NM_001146156.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.153

Variant links:

Genes affected

GSK3B (HGNC:4617): (glycogen synthase kinase 3 beta) The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

GSK3B links:

GSK3B (HGNC:):

GSK3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-120002133-T-A is Benign according to our data. Variant chr3-120002133-T-A is described in ClinVar as [Benign]. Clinvar id is 1276817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2 linkuse as main transcript	c.195A>T	p.Gly65Gly	synonymous_variant	2/11	ENST00000264235.13	NP_001139628.1	P49841-1Q6FI27
GSK3B	NM_002093.4 linkuse as main transcript	c.195A>T	p.Gly65Gly	synonymous_variant	2/12		NP_002084.2	P49841-2
GSK3B	NM_001354596.2 linkuse as main transcript	c.195A>T	p.Gly65Gly	synonymous_variant	2/10		NP_001341525.1
GSK3B	XM_006713610.4 linkuse as main transcript	c.195A>T	p.Gly65Gly	synonymous_variant	2/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13 linkuse as main transcript	c.195A>T	p.Gly65Gly	synonymous_variant	2/11	1	NM_001146156.2	ENSP00000264235.9		P49841-1

Frequencies

GnomAD3 genomes

AF:

0.0601

AC:

9133

AN:

152066

Hom.:

883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0398

GnomAD3 exomes

AF:

0.0162

AC:

4042

AN:

250122

Hom.:

388

AF XY:

0.0121

AC XY:

1638

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.00891

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00229

Gnomad SAS exome

AF:

0.00528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000865

Gnomad OTH exome

AF:

0.00689

GnomAD4 exome

AF:

0.00720

AC:

10509

AN:

1460180

Hom.:

820

Cov.:

AF XY:

0.00636

AC XY:

4623

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.000881

Gnomad4 EAS exome

AF:

0.0266

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000541

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0602

AC:

9158

AN:

152182

Hom.:

888

Cov.:

AF XY:

0.0580

AC XY:

4313

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0394

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0687

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000895

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

DANN

Benign

0.73

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

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