3-120002344-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001146156.2(GSK3B):c.89-106_89-105insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 434,992 control chromosomes in the GnomAD database, including 886 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (590 hom., cov: 30)
  • Exomes 𝑓: 0.13 (296 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.718

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 -10 ACMG points.

• BP6: Variant 3-120002344-A-AT is Benign according to our data. Variant chr3-120002344-A-AT is described in ClinVar as [Benign]. Clinvar id is 1281665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-106_89-105insA		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-106_89-105insA		intron_variant
GSK3B	NM_002093.4	c.89-106_89-105insA		intron_variant
GSK3B	XM_006713610.4	c.89-106_89-105insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-106_89-105insA		intron_variant		1	NM_001146156.2	A1
	ENST00000678483.1	n.31-33272_31-33271insA		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12058 AN: 148100 Hom.: 590 Cov.: 30

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0968

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.126 AC: 36070 AN: 286806 Hom.: 296 AF XY: 0.126 AC XY: 18419 AN XY: 145866

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0565

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.0814 AC: 12060 AN: 148186 Hom.: 590 Cov.: 30 AF XY: 0.0787 AC XY: 5686 AN XY: 72242

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000788

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.101

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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs200371314; hg19: chr3-119721191;