3-120039202-A-G

Variant names:

• chr3-120039202-A-G
• rs6781942
• NM_001146156.2:c.89-36963T>C

Variant summary

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

The NM_001146156.2(GSK3B):​c.89-36963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,090 control chromosomes in the GnomAD database, including 24,722 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 0.53 (24722 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 4 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

ENSG00000288662 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 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.89-36963T>C		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.89-36963T>C		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.89-36963T>C		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.89-36963T>C		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.89-36963T>C		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.89-36963T>C		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80322 AN: 151972 Hom.: 24663 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.529 AC: 80443 AN: 152090 Hom.: 24722 Cov.: 32 AF XY: 0.526 AC XY: 39134 AN XY: 74340

African (AFR) AF: 0.862 AC: 35807 AN: 41520

American (AMR) AF: 0.407 AC: 6222 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3013 AN: 5168

South Asian (SAS) AF: 0.497 AC: 2399 AN: 4824

European-Finnish (FIN) AF: 0.375 AC: 3956 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26117 AN: 67972

Other (OTH) AF: 0.510 AC: 1079 AN: 2114

Alfa AF: 0.493 Hom.: 2728

Bravo AF: 0.542

Asia WGS AF: 0.561 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.61
PhyloP100		-0.15
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: rs6781942; hg19: chr3-119758049;