rs2345994

Variant names:

• chr1-243768973-T-C
• rs2345994
• NM_005465.7:c.47-73257A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-243768973-T-C
• chr1-243768973-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: G2P
• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae)
• megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKT3	NM_005465.7	c.47-73257A>G		intron_variant	Intron 2 of 13	ENST00000673466.1	NP_005456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466.1	c.47-73257A>G		intron_variant	Intron 2 of 13		NM_005465.7	ENSP00000500582.1

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

African (AFR) AF: 0.136 AC: 5638 AN: 41448

American (AMR) AF: 0.598 AC: 9117 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2589 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2165 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2189 AN: 4820

European-Finnish (FIN) AF: 0.598 AC: 6296 AN: 10520

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46024 AN: 67964

Other (OTH) AF: 0.541 AC: 1138 AN: 2102

Alfa AF: 0.615 Hom.: 14091

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
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2345994; hg19: chr1-243932275;