3-119823277-A-T

Position:

• chr3-119823277-A-T

Variant summary

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

The NM_001146156.2(GSK3B):​c.*3511T>A 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 215,980 control chromosomes in the GnomAD database, including 7,090 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 (4957 hom., cov: 32)
  • Exomes 𝑓: 0.24 (2133 hom.)
• Consequence: GSK3B NM_001146156.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.*3511T>A		3_prime_UTR_variant	11/11	ENST00000264235.13
GSK3B	NM_001354596.2	c.*3511T>A		3_prime_UTR_variant	10/10
GSK3B	NM_002093.4	c.*3511T>A		3_prime_UTR_variant	12/12
GSK3B	XM_006713610.4	c.*3511T>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.*3511T>A		3_prime_UTR_variant	11/11	1	NM_001146156.2	A1
GSK3B	ENST00000316626.6	c.*3511T>A		3_prime_UTR_variant	12/12	1		P3
GSK3B	ENST00000678439.1	c.*3511T>A		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36911 AN: 152010 Hom.: 4952 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.239 AC: 15238 AN: 63852 Hom.: 2133 Cov.: 0 AF XY: 0.240 AC XY: 7088 AN XY: 29490

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.243 AC: 36961 AN: 152128 Hom.: 4957 Cov.: 32 AF XY: 0.247 AC XY: 18347 AN XY: 74400

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.227

Alfa AF: 0.227 Hom.: 522

Bravo AF: 0.241

Asia WGS AF: 0.362 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.8
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60393216; hg19: chr3-119542124;