19-42236901-T-C

Position:

• chr19-42236901-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000222330.8(GSK3A):​c.512A>G​(p.Asn171Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSK3A ENST00000222330.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3A	NM_019884.3	c.512A>G	p.Asn171Ser	missense_variant	3/11	ENST00000222330.8	NP_063937.2
GSK3A	XR_001753673.2	n.649A>G		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3A	ENST00000222330.8	c.512A>G	p.Asn171Ser	missense_variant	3/11	1	NM_019884.3	ENSP00000222330	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.8	D;D;.
REVEL	Uncertain	0.52
Sift	Uncertain	0.016	D;D;.
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.87
MutPred		0.91		Gain of MoRF binding (P = 0.1101);.;.;
MVP		0.75
MPC		1.9
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.44
gMVP		0.91

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: chr19-42741053;