Variant chr3-119863444-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001146156.2(GSK3B):c.1071T>C(p.Pro357=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,613,898 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 62 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 62 hom. )

Consequence

GSK3B
NM_001146156.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.29

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 3-119863444-A-G is Benign according to our data. Variant chr3-119863444-A-G is described in ClinVar as [Benign]. Clinvar id is 784016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSK3B	NM_001146156.2 linkuse as main transcript	c.1071T>C	p.Pro357=	synonymous_variant	9/11	ENST00000264235.13
GSK3B	NM_002093.4 linkuse as main transcript	c.1110T>C	p.Pro370=	synonymous_variant	10/12
GSK3B	NM_001354596.2 linkuse as main transcript	c.1071T>C	p.Pro357=	synonymous_variant	9/10
GSK3B	XM_006713610.4 linkuse as main transcript	c.1110T>C	p.Pro370=	synonymous_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13 linkuse as main transcript	c.1071T>C	p.Pro357=	synonymous_variant	9/11	1	NM_001146156.2	A1	P49841-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2413

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00457

AC:

1149

AN:

251436

Hom.:

AF XY:

0.00349

AC XY:

474

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0595

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00186

AC:

2719

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1175

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0585

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000270

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.0159

AC:

2416

AN:

152294

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1128

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0550

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00754

Hom.:

Bravo

AF:

0.0186

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

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