chr3-120002389-T-A

Position:

• chr3-120002389-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146156.2(GSK3B):​c.89-150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 416,424 control chromosomes in the GnomAD database, including 1,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (888 hom., cov: 32)
  • Exomes 𝑓: 0.011 (189 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.299

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-120002389-T-A is Benign according to our data. Variant chr3-120002389-T-A is described in ClinVar as [Benign]. Clinvar id is 1225859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-150A>T		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-150A>T		intron_variant
GSK3B	NM_002093.4	c.89-150A>T		intron_variant
GSK3B	XM_006713610.4	c.89-150A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-150A>T		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.31-33316A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9108 AN: 151974 Hom.: 883 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.0110 AC: 2912 AN: 264332 Hom.: 189 AF XY: 0.00954 AC XY: 1293 AN XY: 135534

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.0171

Gnomad4 ASJ exome AF: 0.000647

Gnomad4 EAS exome AF: 0.0389

Gnomad4 SAS exome AF: 0.00468

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000755

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0601 AC: 9134 AN: 152092 Hom.: 888 Cov.: 32 AF XY: 0.0579 AC XY: 4304 AN XY: 74374

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0394

Alfa AF: 0.0449 Hom.: 65

Bravo AF: 0.0687

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.18

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: rs113113643; hg19: chr3-119721236;