rs6429429

Variant names:

• chr1-243546840-G-T
• rs6429429
• NM_005465.7:c.1164-1243C>A

Variant summary

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

The NM_005465.7(AKT3):​c.1164-1243C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 152,284 control chromosomes in the GnomAD database, including 69,098 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 0.95 (69097 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: AKT3 NM_005465.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 1 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, Labcorp Genetics (formerly Invitae), Illumina
• megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000236031 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKT3	NM_005465.7	MANE Select	c.1164-1243C>A		intron	N/A	NP_005456.1	Q9Y243-1
	AKT3	NM_001370074.1		c.1164-1243C>A		intron	N/A	NP_001357003.1	Q9Y243-1
	AKT3	NM_001206729.2		c.1164-1243C>A		intron	N/A	NP_001193658.1	Q9Y243-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKT3	ENST00000673466.1	MANE Select	c.1164-1243C>A		intron	N/A	ENSP00000500582.1	Q9Y243-1
	AKT3	ENST00000263826.12	TSL:1	c.1164-1243C>A		intron	N/A	ENSP00000263826.5	Q9Y243-1
	AKT3	ENST00000336199.9	TSL:1	c.1164-1243C>A		intron	N/A	ENSP00000336943.5	Q9Y243-2

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144458 AN: 152164 Hom.: 69056 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.965

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.949 AC: 144558 AN: 152282 Hom.: 69097 Cov.: 33 AF XY: 0.951 AC XY: 70817 AN XY: 74454

African (AFR) AF: 0.824 AC: 34210 AN: 41504

American (AMR) AF: 0.979 AC: 14975 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4831 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68012 AN: 68040

Other (OTH) AF: 0.965 AC: 2042 AN: 2116

Alfa AF: 0.976 Hom.: 25072

Bravo AF: 0.941

Asia WGS AF: 0.991 AC: 3441 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.36
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: rs6429429; hg19: chr1-243710142;