1-243500591-C-T

Position:

• chr1-243500591-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.*4658G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 228,610 control chromosomes in the GnomAD database, including 4,191 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 0.17 (2599 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1592 hom.)
• Consequence: AKT3 NM_005465.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

AKT3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT3	NM_005465.7	c.*4658G>A		3_prime_UTR_variant	14/14	ENST00000673466.1	NP_005456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466	c.*4658G>A		3_prime_UTR_variant	14/14		NM_005465.7	ENSP00000500582.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26141 AN: 151940 Hom.: 2599 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.198 AC: 15127 AN: 76552 Hom.: 1592 Cov.: 0 AF XY: 0.197 AC XY: 6930 AN XY: 35216

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.172 AC: 26141 AN: 152058 Hom.: 2599 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74296

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.174

Alfa AF: 0.190 Hom.: 770

Bravo AF: 0.167

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.65

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: rs14403; hg19: chr1-243663893;