19-42242287-A-C

Position:

• chr19-42242287-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019884.3(GSK3A):​c.179T>G​(p.Val60Gly) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSK3A NM_019884.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

GSK3A (HGNC:4616): (glycogen synthase kinase 3 alpha) This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]

ENSG00000268643 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24161172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3A	NM_019884.3	c.179T>G	p.Val60Gly	missense_variant	1/11	ENST00000222330.8	NP_063937.2
GSK3A	XR_001753673.2	n.316T>G		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3A	ENST00000222330.8	c.179T>G	p.Val60Gly	missense_variant	1/11	1	NM_019884.3	ENSP00000222330.3
ENSG00000268643	ENST00000594664.1	c.23-2145T>G		intron_variant		3		ENSP00000470087.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.179T>G (p.V60G) alteration is located in exon 1 (coding exon 1) of the GSK3A gene. This alteration results from a T to G substitution at nucleotide position 179, causing the valine (V) at amino acid position 60 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.54	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.32
Sift	Benign	0.26	T
Sift4G	Benign	0.094	T
Polyphen		0.010	B
Vest4		0.33
MutPred		0.32		Loss of sheet (P = 0.0084);
MVP		0.80
MPC		1.3
ClinPred		0.28	T
GERP RS		-0.59
Varity_R		0.21
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-42746439;