rs2034915

Variant names:

• chr1-243715201-A-G
• rs2034915
• NM_005465.7:c.47-19485T>C

Variant summary

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

The NM_005465.7(AKT3):​c.47-19485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,912 control chromosomes in the GnomAD database, including 23,793 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 (23793 hom., cov: 31)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 5 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

ENSG00000232184 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005465.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKT3	NM_005465.7	MANE Select	c.47-19485T>C		intron	N/A	NP_005456.1
	AKT3	NM_001370074.1		c.47-19485T>C		intron	N/A	NP_001357003.1
	AKT3	NM_001206729.2		c.47-19485T>C		intron	N/A	NP_001193658.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKT3	ENST00000673466.1	MANE Select	c.47-19485T>C		intron	N/A	ENSP00000500582.1
	AKT3	ENST00000263826.12	TSL:1	c.47-19485T>C		intron	N/A	ENSP00000263826.5
	AKT3	ENST00000336199.9	TSL:1	c.47-19485T>C		intron	N/A	ENSP00000336943.5

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77920 AN: 151794 Hom.: 23794 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.513 AC: 77921 AN: 151912 Hom.: 23793 Cov.: 31 AF XY: 0.510 AC XY: 37892 AN XY: 74264

African (AFR) AF: 0.170 AC: 7066 AN: 41476

American (AMR) AF: 0.600 AC: 9155 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2569 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2201 AN: 5160

South Asian (SAS) AF: 0.473 AC: 2272 AN: 4800

European-Finnish (FIN) AF: 0.606 AC: 6406 AN: 10564

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46230 AN: 67858

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.639 Hom.: 18839

Bravo AF: 0.497

Asia WGS AF: 0.398 AC: 1386 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		1.9
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: rs2034915; hg19: chr1-243878503;