dbSNP rs6429429: AKT3:c.1164-1243C>A (chr1-243546840-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.360

Publications

1 publications found

Variant links:

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

AKT3 links:

ENSG00000236031 (HGNC:):

ENSG00000236031 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT3	NM_005465.7 link	c.1164-1243C>A		intron_variant	Intron 11 of 13	ENST00000673466.1	NP_005456.1	Q9Y243-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKT3	ENST00000673466.1 link	c.1164-1243C>A		intron_variant	Intron 11 of 13		NM_005465.7	ENSP00000500582.1		Q9Y243-1

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

144458

AN:

152164

Hom.:

69056

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.949

AC:

144558

AN:

152282

Hom.:

69097

Cov.:

AF XY:

0.951

AC XY:

70817

AN XY:

74454

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

335

670

1005

1340

1675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.5

(source)

DANN

Benign

0.58

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over