rs2291409

Variant names:

• chr1-243568895-G-A
• rs2291409
• NM_005465.7:c.819+4031C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-243568895-G-A
• chr1-243568895-G-C
• chr1-243568895-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005465.7(AKT3):​c.819+4031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,992 control chromosomes in the GnomAD database, including 23,926 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 (23926 hom., cov: 32)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 8 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=-0.87).
• 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 rank	MANE	Protein	UniProt
AKT3	NM_005465.7	c.819+4031C>T		intron_variant	Intron 9 of 13	ENST00000673466.1	NP_005456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466.1	c.819+4031C>T		intron_variant	Intron 9 of 13		NM_005465.7	ENSP00000500582.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78694 AN: 151876 Hom.: 23926 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.518 AC: 78702 AN: 151992 Hom.: 23926 Cov.: 32 AF XY: 0.515 AC XY: 38272 AN XY: 74266

African (AFR) AF: 0.184 AC: 7631 AN: 41468

American (AMR) AF: 0.601 AC: 9180 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2504 AN: 5166

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4816

European-Finnish (FIN) AF: 0.618 AC: 6499 AN: 10518

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46130 AN: 67978

Other (OTH) AF: 0.562 AC: 1187 AN: 2112

Alfa AF: 0.524 Hom.: 4045

Bravo AF: 0.501

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.87
DANN	Benign	0.77
PhyloP100		-0.77
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: rs2291409; hg19: chr1-243732197;