3-120085289-G-C

Variant names:

• chr3-120085289-G-C
• rs334555
• NM_001146156.2:c.88+8058C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.88+8058C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,232 control chromosomes in the GnomAD database, including 61,144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (61144 hom., cov: 31)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.88+8058C>G		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.88+8058C>G		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.88+8058C>G		intron	N/A	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.88+8058C>G		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.88+8058C>G		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.88+8058C>G		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135965 AN: 152114 Hom.: 61079 Cov.: 31

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.894 AC: 136090 AN: 152232 Hom.: 61144 Cov.: 31 AF XY: 0.897 AC XY: 66788 AN XY: 74420

African (AFR) AF: 0.971 AC: 40352 AN: 41548

American (AMR) AF: 0.897 AC: 13722 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2709 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.979 AC: 4723 AN: 4826

European-Finnish (FIN) AF: 0.874 AC: 9244 AN: 10580

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57400 AN: 68014

Other (OTH) AF: 0.872 AC: 1844 AN: 2114

Alfa AF: 0.846 Hom.: 2672

Bravo AF: 0.896

Asia WGS AF: 0.978 AC: 3400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs334555; hg19: chr3-119804136;