chr3-119876470-C-G

Position:

• chr3-119876470-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001146156.2(GSK3B):​c.852G>C​(p.Met284Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSK3B NM_001146156.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.852G>C	p.Met284Ile	missense_variant	8/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.852G>C	p.Met284Ile	missense_variant	8/12		NP_002084.2
GSK3B	NM_001354596.2	c.852G>C	p.Met284Ile	missense_variant	8/10		NP_001341525.1
GSK3B	XM_006713610.4	c.852G>C	p.Met284Ile	missense_variant	8/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.852G>C	p.Met284Ile	missense_variant	8/11	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.91	L;L;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.0030	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.59
MutPred		0.46		Gain of glycosylation at T289 (P = 0.0122);Gain of glycosylation at T289 (P = 0.0122);Gain of glycosylation at T289 (P = 0.0122);
MVP		0.85
MPC		1.9
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.88
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-119595317;