rs3745233

Positions:

• chr19-42229713-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000677025.1(GSK3A):​c.93+2344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,128 control chromosomes in the GnomAD database, including 1,317 homozygotes. 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: 𝑓 0.12 (1317 hom., cov: 32)
• Consequence: GSK3A ENST00000677025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSK3A	ENST00000677025.1	c.93+2344A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18514 AN: 152010 Hom.: 1302 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0910

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18569 AN: 152128 Hom.: 1317 Cov.: 32 AF XY: 0.121 AC XY: 8966 AN XY: 74358

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0904

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.132

Alfa AF: 0.111 Hom.: 998

Bravo AF: 0.131

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745233; hg19: chr19-42733865;