7-92079584-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005751.5(AKAP9):c.7451A>G(p.Lys2484Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,678 control chromosomes in the GnomAD database, including 13,938 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 984 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12954 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.723

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012037754).

BP6

Variant 7-92079584-A-G is Benign according to our data. Variant chr7-92079584-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 136338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92079584-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.7451A>G	p.Lys2484Arg	missense_variant	Exon 31 of 50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.7427A>G	p.Lys2476Arg	missense_variant	Exon 31 of 50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7
AKAP9	NM_001379277.1 link	c.2096A>G	p.Lys699Arg	missense_variant	Exon 10 of 29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.7451A>G	p.Lys2484Arg	missense_variant	Exon 31 of 50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15253

AN:

152164

Hom.:

985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.0998

GnomAD3 exomes

AF:

0.107

AC:

26831

AN:

249680

Hom.:

1726

AF XY:

0.110

AC XY:

14926

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.0589

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0271

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.129

AC:

188791

AN:

1461396

Hom.:

12954

Cov.:

AF XY:

0.130

AC XY:

94146

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.0258

Gnomad4 AMR exome

AF:

0.0617

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.0168

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.100

AC:

15249

AN:

152282

Hom.:

984

Cov.:

AF XY:

0.0994

AC XY:

7399

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0286

Gnomad4 AMR

AF:

0.0794

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0282

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.126

Hom.:

1856

Bravo

AF:

0.0901

TwinsUK

AF:

0.140

AC:

519

ALSPAC

AF:

0.135

AC:

520

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.127

AC:

1095

ExAC

AF:

0.108

AC:

13143

Asia WGS

AF:

0.0930

AC:

323

AN:

3476

EpiCase

AF:

0.139

EpiControl

AF:

0.137

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 08, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 26, 2020

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Long QT syndrome 11

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 21, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0020

DANN

Benign

0.39

DEOGEN2

Benign

0.23

.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.41

T;T;T;T

MetaRNN

Benign

0.0012

T;T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.27

N;.;.;N

REVEL

Benign

0.0070

Sift

Benign

0.55

T;.;.;T

Sift4G

Benign

0.40

.;T;.;T

Vest4

0.047

MPC

0.046

ClinPred

0.0014

GERP RS

-8.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.062

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over