19-42229713-T-C

Variant names:

• chr19-42229713-T-C
• rs3745233
• ENST00000678490.1:c.91+2344A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000678490.1(ENSG00000288671):​c.91+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: ENSG00000288671 ENST00000678490.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 8 publications found

Genes affected

ENSG00000288671 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288671	ENST00000678490.1	c.91+2344A>G		intron_variant	Intron 1 of 1			ENSP00000502878.1
GSK3A	ENST00000677025.1	c.91+2344A>G		intron_variant	Intron 1 of 1			ENSP00000503204.1

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

African (AFR) AF: 0.166 AC: 6895 AN: 41484

American (AMR) AF: 0.130 AC: 1983 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.0904 AC: 468 AN: 5176

South Asian (SAS) AF: 0.181 AC: 872 AN: 4822

European-Finnish (FIN) AF: 0.0514 AC: 545 AN: 10604

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7033 AN: 67968

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.113 Hom.: 1323

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
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs3745233; hg19: chr19-42733865;