NM_005751.5:c.2425A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_005751.5(AKAP9):c.2425A>G(p.Ile809Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,612,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I809F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.140

Publications

5 publications found

Variant links:

Genes affected

AKAP9 (HGNC:379): (A-kinase anchoring protein 9) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternate splicing of this gene results in at least two isoforms that localize to the centrosome and the Golgi apparatus, and interact with numerous signaling proteins from multiple signal transduction pathways. These signaling proteins include type II protein kinase A, serine/threonine kinase protein kinase N, protein phosphatase 1, protein phosphatase 2a, protein kinase C-epsilon and phosphodiesterase 4D3. [provided by RefSeq, Aug 2008]

AKAP9 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
long QT syndrome 11
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
long QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

AKAP9 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 (MetaRNN=0.0034397542).

BP6

Variant 7-92002342-A-G is Benign according to our data. Variant chr7-92002342-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 190506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005751.5. 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
	AKAP9	NM_005751.5	MANE Select	c.2425A>G	p.Ile809Val	missense	Exon 8 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.2425A>G	p.Ile809Val	missense	Exon 8 of 50	NP_671714.1	Q99996-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.2425A>G	p.Ile809Val	missense	Exon 8 of 50	ENSP00000348573.3	Q99996-2
AKAP9	ENST00000359028.7	TSL:5	c.2425A>G	p.Ile809Val	missense	Exon 8 of 51	ENSP00000351922.4	A0A0A0MRF6
AKAP9	ENST00000681412.1		c.2425A>G	p.Ile809Val	missense	Exon 8 of 49	ENSP00000506486.1	A0A7P0TBH8

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.000606

AC:

152

AN:

250678

AF XY:

0.000553

show subpopulations

Gnomad AFR exome

AF:

0.00879

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000266

AC:

388

AN:

1460880

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

726732

show subpopulations

African (AFR)

AF:

0.00942

AC:

315

AN:

33442

American (AMR)

AF:

0.000246

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39556

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111516

Other (OTH)

AF:

0.000564

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00266

AC:

405

AN:

152110

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00941

AC:

391

AN:

41562

American (AMR)

AF:

0.000393

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67858

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000930

Hom.:

Bravo

AF:

0.00284

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Long QT syndrome 11 (2)

not specified (2)

AKAP9-related disorder (1)

Cardiovascular phenotype (1)

Long QT syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.64

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.24

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.61

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.92

PhyloP100

-0.14

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.25

REVEL

Benign

0.031

Sift

Benign

0.55

Sift4G

Benign

0.40

Vest4

0.033

MVP

0.17

MPC

0.047

ClinPred

0.0045

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.069

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over