3-120094435-A-G

Position:

• chr3-120094435-A-G

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.-1001T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 296,038 control chromosomes in the GnomAD database, including 38,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23682 hom., cov: 33)
  • Exomes 𝑓: 0.44 (14698 hom.)
• Consequence: GSK3B NM_001146156.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-120094435-A-G is Benign according to our data. Variant chr3-120094435-A-G is described in ClinVar as [Benign]. Clinvar id is 1258187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.-1001T>C		5_prime_UTR_variant	1/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.-1001T>C		5_prime_UTR_variant	1/12		NP_002084.2
GSK3B	NM_001354596.2	c.-1001T>C		5_prime_UTR_variant	1/10		NP_001341525.1
GSK3B	XM_006713610.4	c.-1001T>C		5_prime_UTR_variant	1/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.-1001T>C		5_prime_UTR_variant	1/11	1	NM_001146156.2	ENSP00000264235.9
GSK3B	ENST00000677034.1	c.-1001T>C		5_prime_UTR_variant	1/3			ENSP00000504055.1
GSK3B	ENST00000677338.1	c.-160+531T>C		intron_variant				ENSP00000503497.1
GSK3B	ENST00000677903.1	c.-160+108T>C		intron_variant				ENSP00000503112.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77646 AN: 151950 Hom.: 23628 Cov.: 33

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.438 AC: 63023 AN: 143972 Hom.: 14698 Cov.: 0 AF XY: 0.444 AC XY: 35308 AN XY: 79534

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.511 AC: 77762 AN: 152066 Hom.: 23682 Cov.: 33 AF XY: 0.510 AC XY: 37939 AN XY: 74348

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.491

Alfa AF: 0.375 Hom.: 11825

Bravo AF: 0.522

Asia WGS AF: 0.594 AC: 2055 AN: 3468

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	This variant is associated with the following publications: (PMID: 14729229, 11326302, 21527318) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs334558; hg19: chr3-119813282;