Variant 3-120002229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001146156.2(GSK3B):c.99C>T(p.Asp33=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000125 in 1,548,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

GSK3B
NM_001146156.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.16

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-120002229-G-A is Benign according to our data. Variant chr3-120002229-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718992.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSK3B	NM_001146156.2 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	2/11	ENST00000264235.13
GSK3B	NM_002093.4 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	2/12
GSK3B	NM_001354596.2 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	2/10
GSK3B	XM_006713610.4 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	2/11	1	NM_001146156.2	A1	P49841-1
	ENST00000678483.1 linkuse as main transcript	n.31-33156C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

203032

Hom.:

AF XY:

0.0000902

AC XY:

AN XY:

110888

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.0000457

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000423

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

163

AN:

1395922

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

692156

show subpopulations

Gnomad4 AFR exome

AF:

0.000267

Gnomad4 AMR exome

AF:

0.0000599

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000629

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000996

Gnomad4 OTH exome

AF:

0.000383

GnomAD4 genome

AF:

0.000204

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000196

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.64

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