chr1-243839471-C-T

Position:

• chr1-243839471-C-T

Variant summary

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

The NM_005465.7(AKT3):​c.46+3654G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,994 control chromosomes in the GnomAD database, including 23,522 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 0.51 (23522 hom., cov: 32)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT3	NM_005465.7	c.46+3654G>A		intron_variant		ENST00000673466.1	NP_005456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466.1	c.46+3654G>A		intron_variant			NM_005465.7	ENSP00000500582	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76789 AN: 151876 Hom.: 23520 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.505 AC: 76790 AN: 151994 Hom.: 23522 Cov.: 32 AF XY: 0.502 AC XY: 37330 AN XY: 74302

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.548

Alfa AF: 0.555 Hom.: 3726

Bravo AF: 0.488

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.43

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: rs4590656; hg19: chr1-244002773;