rs6960867

Positions:

Variant summary

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

The NM_005751.5(AKAP9):c.8375A>G(p.Asn2792Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,613,262 control chromosomes in the GnomAD database, including 116,125 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 0.34 ( 9247 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106878 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.334

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=5.6543946E-4).

BP6

Variant 7-92083384-A-G is Benign according to our data. Variant chr7-92083384-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 136340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92083384-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKAP9	NM_005751.5 linkuse as main transcript	c.8375A>G	p.Asn2792Ser	missense_variant	33/50	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3 linkuse as main transcript	c.8351A>G	p.Asn2784Ser	missense_variant	33/50		NP_671714.1
AKAP9	NM_001379277.1 linkuse as main transcript	c.3020A>G	p.Asn1007Ser	missense_variant	12/29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.8375A>G	p.Asn2792Ser	missense_variant	33/50	1	NM_005751.5	ENSP00000348573	P4	Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51609

AN:

151960

Hom.:

9249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.359

AC:

89641

AN:

249908

Hom.:

16845

AF XY:

0.366

AC XY:

49453

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.546

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.379

AC:

553710

AN:

1461184

Hom.:

106878

Cov.:

AF XY:

0.380

AC XY:

276338

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.339

AC:

51620

AN:

152078

Hom.:

9247

Cov.:

AF XY:

0.339

AC XY:

25231

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.386

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.381

Hom.:

19570

Bravo

AF:

0.331

TwinsUK

AF:

0.377

AC:

1397

ALSPAC

AF:

0.392

AC:

1511

ESP6500AA

AF:

0.268

AC:

1180

ESP6500EA

AF:

0.401

AC:

3451

ExAC

AF:

0.359

AC:

43538

Asia WGS

AF:

0.294

AC:

1026

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.402

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 11, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2011	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jun 24, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Long QT syndrome 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2015

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

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.81

DEOGEN2

Benign

0.27

.;T;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.77

T;T;T;T

MetaRNN

Benign

0.00057

T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.0

N;.;.;N

REVEL

Benign

0.070

Sift

Benign

0.23

T;.;.;T

Sift4G

Benign

0.87

.;T;.;T

Vest4

0.061

MPC

0.046

ClinPred

0.0056

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.078

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