3-120002324-T-C

Position:

• chr3-120002324-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146156.2(GSK3B):​c.89-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 611,412 control chromosomes in the GnomAD database, including 17,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4880 hom., cov: 32)
  • Exomes 𝑓: 0.21 (12244 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0200

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]

ENSG00000288662 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-120002324-T-C is Benign according to our data. Variant chr3-120002324-T-C is described in ClinVar as [Benign]. Clinvar id is 1222554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.89-85A>G		intron_variant		ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.89-85A>G		intron_variant			NP_002084.2
GSK3B	NM_001354596.2	c.89-85A>G		intron_variant			NP_001341525.1
GSK3B	XM_006713610.4	c.89-85A>G		intron_variant			XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-85A>G		intron_variant		1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36654 AN: 151674 Hom.: 4876 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.213 AC: 98056 AN: 459620 Hom.: 12244 AF XY: 0.214 AC XY: 50627 AN XY: 236448

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.242 AC: 36701 AN: 151792 Hom.: 4880 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74182

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.227

Alfa AF: 0.216 Hom.: 480

Bravo AF: 0.239

Asia WGS AF: 0.366 AC: 1270 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.33
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs12108149; hg19: chr3-119721171;