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GeneBe

3-119923394-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.669 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 610 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSK3BNM_001146156.2 linkuse as main transcriptc.456G>A p.Thr152= synonymous_variant 4/11 ENST00000264235.13
GSK3BNM_002093.4 linkuse as main transcriptc.456G>A p.Thr152= synonymous_variant 4/12
GSK3BNM_001354596.2 linkuse as main transcriptc.456G>A p.Thr152= synonymous_variant 4/10
GSK3BXM_006713610.4 linkuse as main transcriptc.456G>A p.Thr152= synonymous_variant 4/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSK3BENST00000264235.13 linkuse as main transcriptc.456G>A p.Thr152= synonymous_variant 4/111 NM_001146156.2 A1P49841-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00401
AC:
610
AN:
152014
Hom.:
2
Cov.:
32
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.:
2
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.:
6
Cov.:
25
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00404
AC:
615
AN:
152132
Hom.:
2
Cov.:
32
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.:
0
Bravo
AF:
0.00477

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
11
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.

Other links and lift over

dbSNP: rs17183890; hg19: chr3-119642241; COSMIC: COSV99955201; API