rs2345994

chr1-243768973-T-Cchr1-243768973-T-G

Variant summary

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

The NM_005465.7(AKT3):c.47-73257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,944 control chromosomes in the GnomAD database, including 23,309 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 0.50 (23309 hom., cov: 31)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

AKT3 (HGNC:393): (AKT serine/threonine kinase 3) The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT3	NM_005465.7	c.47-73257A>G		intron_variant		ENST00000673466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT3	ENST00000673466.1	c.47-73257A>G		intron_variant			NM_005465.7	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76001 AN: 151826 Hom.: 23307 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.500 AC: 75998 AN: 151944 Hom.: 23309 Cov.: 31 AF XY: 0.497 AC XY: 36906 AN XY: 74254

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.541

Alfa AF: 0.609 Hom.: 12368

Bravo AF: 0.483

Asia WGS AF: 0.382 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.3
Dann	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs2345994; hg19: chr1-243932275;