1-243554290-A-T

Position:

• chr1-243554290-A-T

Variant summary

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

The NM_005465.7(AKT3):​c.949-1347T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,026 control chromosomes in the GnomAD database, including 24,172 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 0.52 (24172 hom., cov: 32)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKT3	NM_005465.7	c.949-1347T>A		intron_variant		ENST00000673466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKT3	ENST00000673466.1	c.949-1347T>A		intron_variant			NM_005465.7	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79766 AN: 151908 Hom.: 24172 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.525 AC: 79777 AN: 152026 Hom.: 24172 Cov.: 32 AF XY: 0.522 AC XY: 38808 AN XY: 74296

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.568

Alfa AF: 0.584 Hom.: 3496

Bravo AF: 0.509

Asia WGS AF: 0.420 AC: 1455 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.61

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: rs2220276; hg19: chr1-243717592;