rs334558

Positions:

• chr3-120094435-A-C
• chr3-120094435-A-G
• chr3-120094435-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146156.2(GSK3B):​c.-1001T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: GSK3B NM_001146156.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.-1001T>G		5_prime_UTR_variant	1/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_001354596.2	c.-1001T>G		5_prime_UTR_variant	1/10		NP_001341525.1
GSK3B	NM_002093.4	c.-1001T>G		5_prime_UTR_variant	1/12		NP_002084.2
GSK3B	XM_006713610.4	c.-1001T>G		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>G		5_prime_UTR_variant	1/11	1	NM_001146156.2	ENSP00000264235	A1
GSK3B	ENST00000677034.1	c.-1001T>G		5_prime_UTR_variant	1/3			ENSP00000504055
GSK3B	ENST00000677338.1	c.-160+531T>G		intron_variant				ENSP00000503497
GSK3B	ENST00000677903.1	c.-160+108T>G		intron_variant				ENSP00000503112

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.75

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;