3-119823450-A-G

Position:

• chr3-119823450-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264235.13(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 ENST00000264235.13 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.*3338T>C		3_prime_UTR_variant	11/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_001354596.2	c.*3338T>C		3_prime_UTR_variant	10/10		NP_001341525.1
GSK3B	NM_002093.4	c.*3338T>C		3_prime_UTR_variant	12/12		NP_002084.2
GSK3B	XM_006713610.4	c.*3338T>C		3_prime_UTR_variant	11/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.*3338T>C		3_prime_UTR_variant	11/11	1	NM_001146156.2	ENSP00000264235	A1
GSK3B	ENST00000316626.6	c.*3338T>C		3_prime_UTR_variant	12/12	1		ENSP00000324806	P3
GSK3B	ENST00000678439.1	c.*3338T>C		3_prime_UTR_variant	12/12			ENSP00000503868

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

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.612

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.555

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.500

Alfa AF: 0.581 Hom.: 27076

Bravo AF: 0.485

Asia WGS AF: 0.452 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3732361; hg19: chr3-119542297;