3-120094435-A-T

Variant names:

• chr3-120094435-A-T
• rs334558
• NM_001146156.2:c.-1001T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146156.2(GSK3B):​c.-1001T>A 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSK3B NM_001146156.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 148 publications found

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]

GSK3B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.-1001T>A		5_prime_UTR	Exon 1 of 11	NP_001139628.1	Q6FI27
	GSK3B	NM_002093.4		c.-1001T>A		5_prime_UTR	Exon 1 of 12	NP_002084.2
	GSK3B	NM_001354596.2		c.-1001T>A		5_prime_UTR	Exon 1 of 10	NP_001341525.1	A0A3B3ITW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.-1001T>A		5_prime_UTR	Exon 1 of 11	ENSP00000264235.9	P49841-1
	GSK3B	ENST00000899266.1		c.-1001T>A		5_prime_UTR	Exon 1 of 11	ENSP00000569325.1
	GSK3B	ENST00000899265.1		c.-1001T>A		5_prime_UTR	Exon 1 of 11	ENSP00000569324.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 144552 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 79862

African (AFR) AF: 0.00 AC: 0 AN: 3610

American (AMR) AF: 0.00 AC: 0 AN: 2796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5538

East Asian (EAS) AF: 0.00 AC: 0 AN: 12052

South Asian (SAS) AF: 0.00 AC: 0 AN: 16390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 90648

Other (OTH) AF: 0.00 AC: 0 AN: 9072

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		1.8
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs334558; hg19: chr3-119813282;