3-119823343-G-A

Variant names:

• chr3-119823343-G-A
• rs56728675
• NM_001146156.2:c.*3445C>T

Variant summary

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

The NM_001146156.2(GSK3B):​c.*3445C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 204,540 control chromosomes in the GnomAD database, including 6,742 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 0.24 (4929 hom., cov: 32)
  • Exomes 𝑓: 0.24 (1813 hom.)
• Consequence: GSK3B NM_001146156.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 11 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 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.*3445C>T		3_prime_UTR	Exon 11 of 11	NP_001139628.1
	GSK3B	NM_002093.4		c.*3445C>T		3_prime_UTR	Exon 12 of 12	NP_002084.2
	GSK3B	NM_001354596.2		c.*3445C>T		3_prime_UTR	Exon 10 of 10	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.*3445C>T		3_prime_UTR	Exon 11 of 11	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.*3445C>T		3_prime_UTR	Exon 12 of 12	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.*3445C>T		3_prime_UTR	Exon 12 of 12	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36808 AN: 151942 Hom.: 4925 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.242 AC: 12697 AN: 52478 Hom.: 1813 Cov.: 0 AF XY: 0.242 AC XY: 5912 AN XY: 24414

African (AFR) AF: 0.322 AC: 764 AN: 2374

American (AMR) AF: 0.198 AC: 291 AN: 1470

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 742 AN: 3378

East Asian (EAS) AF: 0.473 AC: 3869 AN: 8182

South Asian (SAS) AF: 0.280 AC: 122 AN: 436

European-Finnish (FIN) AF: 0.267 AC: 8 AN: 30

Middle Eastern (MID) AF: 0.236 AC: 77 AN: 326

European-Non Finnish (NFE) AF: 0.184 AC: 5857 AN: 31900

Other (OTH) AF: 0.221 AC: 967 AN: 4382

GnomAD4 genome AF: 0.242 AC: 36857 AN: 152062 Hom.: 4929 Cov.: 32 AF XY: 0.246 AC XY: 18299 AN XY: 74318

African (AFR) AF: 0.314 AC: 13010 AN: 41448

American (AMR) AF: 0.204 AC: 3113 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2504 AN: 5180

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4818

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12602 AN: 67976

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.212 Hom.: 1538

Bravo AF: 0.240

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.8
DANN	Benign	0.81
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56728675; hg19: chr3-119542190;