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GeneBe

3-120002133-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001146156.2(GSK3B):c.195A>T(p.Gly65=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-120002133-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_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=0.153 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
GSK3BNM_001146156.2 linkuse as main transcriptc.195A>T p.Gly65= synonymous_variant 2/11 ENST00000264235.13
GSK3BNM_002093.4 linkuse as main transcriptc.195A>T p.Gly65= synonymous_variant 2/12
GSK3BNM_001354596.2 linkuse as main transcriptc.195A>T p.Gly65= synonymous_variant 2/10
GSK3BXM_006713610.4 linkuse as main transcriptc.195A>T p.Gly65= synonymous_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSK3BENST00000264235.13 linkuse as main transcriptc.195A>T p.Gly65= synonymous_variant 2/111 NM_001146156.2 A1P49841-1
ENST00000678483.1 linkuse as main transcriptn.31-33060A>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0601
AC:
9133
AN:
152066
Hom.:
883
Cov.:
32
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0602
AC:
9158
AN:
152182
Hom.:
888
Cov.:
32
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.:
77
Bravo
AF:
0.0687
Asia WGS
AF:
0.0220
AC:
77
AN:
3478
EpiCase
AF:
0.00115
EpiControl
AF:
0.000895

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 testingGeneDxJun 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.

Other links and lift over

dbSNP: rs34002644; hg19: chr3-119720980; API