3-119823450-A-G

Variant names:

• chr3-119823450-A-G
• rs3732361
• NM_001146156.2:c.*3338T>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.*3338T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 195,156 control chromosomes in the GnomAD database, including 27,687 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 0.49 (20828 hom., cov: 31)
  • Exomes 𝑓: 0.56 (6859 hom.)
• Consequence: GSK3B NM_001146156.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 29 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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 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.*3338T>C		3_prime_UTR	Exon 11 of 11	NP_001139628.1
	GSK3B	NM_002093.4		c.*3338T>C		3_prime_UTR	Exon 12 of 12	NP_002084.2
	GSK3B	NM_001354596.2		c.*3338T>C		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.*3338T>C		3_prime_UTR	Exon 11 of 11	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.*3338T>C		3_prime_UTR	Exon 12 of 12	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.*3338T>C		3_prime_UTR	Exon 12 of 12	ENSP00000503868.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75110 AN: 151868 Hom.: 20823 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.556 AC: 23980 AN: 43168 Hom.: 6859 Cov.: 0 AF XY: 0.559 AC XY: 11082 AN XY: 19828

African (AFR) AF: 0.201 AC: 377 AN: 1878

American (AMR) AF: 0.612 AC: 719 AN: 1174

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1601 AN: 2784

East Asian (EAS) AF: 0.481 AC: 3521 AN: 7324

South Asian (SAS) AF: 0.517 AC: 182 AN: 352

European-Finnish (FIN) AF: 0.538 AC: 14 AN: 26

Middle Eastern (MID) AF: 0.538 AC: 141 AN: 262

European-Non Finnish (NFE) AF: 0.599 AC: 15471 AN: 25846

Other (OTH) AF: 0.555 AC: 1954 AN: 3522

GnomAD4 genome AF: 0.494 AC: 75141 AN: 151988 Hom.: 20828 Cov.: 31 AF XY: 0.497 AC XY: 36898 AN XY: 74304

African (AFR) AF: 0.229 AC: 9479 AN: 41464

American (AMR) AF: 0.594 AC: 9066 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2021 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2218 AN: 5168

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4808

European-Finnish (FIN) AF: 0.620 AC: 6538 AN: 10550

Middle Eastern (MID) AF: 0.534 AC: 155 AN: 290

European-Non Finnish (NFE) AF: 0.612 AC: 41565 AN: 67950

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.570 Hom.: 34133

Bravo AF: 0.485

Asia WGS AF: 0.452 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-0.67
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: rs3732361; hg19: chr3-119542297;