rs138161478

Positions:

chr7-92001016-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005751.5(AKAP9):c.1099G>A(p.Val367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,565,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:2B:6

Conservation

PhyloP100: -0.108

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:

AKAP9 (HGNC:):

AKAP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008812994).

BP6

Variant 7-92001016-G-A is Benign according to our data. Variant chr7-92001016-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 180260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92001016-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP9	NM_005751.5 linkuse as main transcript	c.1099G>A	p.Val367Met	missense_variant	8/50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 linkuse as main transcript	c.1099G>A	p.Val367Met	missense_variant	8/50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.1099G>A	p.Val367Met	missense_variant	8/50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000346

AC:

AN:

182088

Hom.:

AF XY:

0.000330

AC XY:

AN XY:

97018

show subpopulations

Gnomad AFR exome

AF:

0.0000927

Gnomad AMR exome

AF:

0.0000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000337

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.000367

Gnomad OTH exome

AF:

0.000203

GnomAD4 exome

AF:

0.000379

AC:

536

AN:

1413442

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

237

AN XY:

698928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.0000273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000860

Gnomad4 NFE exome

AF:

0.000414

Gnomad4 OTH exome

AF:

0.000273

GnomAD4 genome

AF:

0.000309

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.000204

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000254

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jun 24, 2013	- -

Long QT syndrome 2

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Blueprint Genetics

May 26, 2014

- -

Cardiac arrest

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Blueprint Genetics

May 26, 2014

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 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. -

Long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 13, 2023

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2018

This alteration is classified as likely 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

0.097

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.7

DANN

Benign

0.48

DEOGEN2

Benign

0.28

.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.62

N;.;.;.

REVEL

Benign

0.055

Sift

Uncertain

0.019

D;.;.;.

Sift4G

Benign

0.20

.;T;T;.

Vest4

0.072

MVP

0.21

MPC

0.059

ClinPred

0.0024

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.072

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