Genetic Variant NM_005465.7:c.562-9546T>G (chr1-243624707-A-C) – 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.562-9546T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 201,814 control chromosomes in the GnomAD database, including 173 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 0.026 ( 113 hom., cov: 31)

Exomes 𝑓: 0.036 ( 60 hom. )

Consequence

AKT3
NM_005465.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

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 links:

FABP7P1 (HGNC:41951): (fatty acid binding protein 7 pseudogene 1)

FABP7P1 links:

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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=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKT3	NM_005465.7 link	c.562-9546T>G		intron_variant	Intron 6 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.562-9546T>G		intron_variant	Intron 6 of 13		NM_005465.7	ENSP00000500582.1		Q9Y243-1

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4016

AN:

152190

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0914

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0303

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0355

AC:

1758

AN:

49506

Hom.:

Cov.:

AF XY:

0.0381

AC XY:

1120

AN XY:

29414

show subpopulations

African (AFR)

AF:

0.00629

AC:

AN:

1272

American (AMR)

AF:

0.00615

AC:

AN:

7318

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

AN:

770

East Asian (EAS)

AF:

0.119

AC:

355

AN:

2972

South Asian (SAS)

AF:

0.0831

AC:

407

AN:

4896

European-Finnish (FIN)

AF:

0.0175

AC:

AN:

4240

Middle Eastern (MID)

AF:

0.0199

AC:

AN:

1206

European-Non Finnish (NFE)

AF:

0.0315

AC:

785

AN:

24956

Other (OTH)

AF:

0.0240

AC:

AN:

1876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.0264

AC:

4018

AN:

152308

Hom.:

113

Cov.:

AF XY:

0.0269

AC XY:

2003

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00544

AC:

226

AN:

41554

American (AMR)

AF:

0.0140

AC:

214

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3468

East Asian (EAS)

AF:

0.128

AC:

664

AN:

5180

South Asian (SAS)

AF:

0.0917

AC:

442

AN:

4820

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0303

AC:

2060

AN:

68040

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0208

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.5

(source)

DANN

Benign

0.63

PhyloP100

-0.57

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