Variant chr3-119923394-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001146156.2(GSK3B):c.456G>A(p.Thr152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,573,904 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 6 hom. )

Consequence

GSK3B
NM_001146156.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.669

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 3-119923394-C-T is Benign according to our data. Variant chr3-119923394-C-T is described in ClinVar as [Benign]. Clinvar id is 721176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.669 with no splicing effect.

BS2

High AC in GnomAd4 at 615 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSK3B	NM_001146156.2 linkuse as main transcript	c.456G>A	p.Thr152=	synonymous_variant	4/11	ENST00000264235.13
GSK3B	NM_002093.4 linkuse as main transcript	c.456G>A	p.Thr152=	synonymous_variant	4/12
GSK3B	NM_001354596.2 linkuse as main transcript	c.456G>A	p.Thr152=	synonymous_variant	4/10
GSK3B	XM_006713610.4 linkuse as main transcript	c.456G>A	p.Thr152=	synonymous_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13 linkuse as main transcript	c.456G>A	p.Thr152=	synonymous_variant	4/11	1	NM_001146156.2	A1	P49841-1

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

610

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00120

AC:

294

AN:

245640

Hom.:

AF XY:

0.000897

AC XY:

119

AN XY:

132646

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.000824

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000501

AC:

713

AN:

1421772

Hom.:

Cov.:

AF XY:

0.000441

AC XY:

313

AN XY:

709308

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.0000779

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000938

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.00404

AC:

615

AN:

152132

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

286

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00477

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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