chr3-120041321-C-T

Position:

• chr3-120041321-C-T

Variant summary

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

The NM_001146156.2(GSK3B):​c.89-39082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 302,540 control chromosomes in the GnomAD database, including 1,684 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 0.10 (946 hom., cov: 31)
  • Exomes 𝑓: 0.089 (738 hom.)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

RFKP3 (HGNC:56487): (RFK pseudogene 3)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSK3B	NM_001146156.2	c.89-39082G>A		intron_variant		ENST00000264235.13
GSK3B	NM_001354596.2	c.89-39082G>A		intron_variant
GSK3B	NM_002093.4	c.89-39082G>A		intron_variant
GSK3B	XM_006713610.4	c.89-39082G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3B	ENST00000264235.13	c.89-39082G>A		intron_variant		1	NM_001146156.2	A1
RFKP3	ENST00000491262.1	n.132C>T		non_coding_transcript_exon_variant	1/1
	ENST00000678483.1	n.30+26854G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15893 AN: 151762 Hom.: 946 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0887 AC: 13361 AN: 150660 Hom.: 738 Cov.: 0 AF XY: 0.0935 AC XY: 8179 AN XY: 87512

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.0820

Gnomad4 EAS exome AF: 0.0802

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0658

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0910

GnomAD4 genome AF: 0.105 AC: 15905 AN: 151880 Hom.: 946 Cov.: 31 AF XY: 0.105 AC XY: 7818 AN XY: 74242

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0711

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.108

Alfa AF: 0.101 Hom.: 130

Bravo AF: 0.105

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.40

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: rs16830683; hg19: chr3-119760168;