rs10644111

chr7-92022864-A-AAAC

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_005751.5(AKAP9):c.4004_4006dup(p.Lys1335_Leu1336insGln) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,603,344 control chromosomes in the GnomAD database, including 129,701 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16438 hom., cov: 0)

Exomes 𝑓: 0.39 ( 113263 hom. )

Consequence

AKAP9
NM_005751.5 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 1.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_005751.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 7-92022864-A-AAAC is Benign according to our data. Variant chr7-92022864-A-AAAC is described in ClinVar as [Likely_benign]. Clinvar id is 190508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP9	NM_005751.5 linkuse as main transcript	c.4004_4006dup	p.Lys1335_Leu1336insGln	inframe_insertion	14/50	ENST00000356239.8
AKAP9	NM_147185.3 linkuse as main transcript	c.4004_4006dup	p.Lys1335_Leu1336insGln	inframe_insertion	14/50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.4004_4006dup	p.Lys1335_Leu1336insGln	inframe_insertion	14/50	1	NM_005751.5	P4	Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68175

AN:

151718

Hom.:

16402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.390

AC:

97595

AN:

250214

Hom.:

20067

AF XY:

0.390

AC XY:

52691

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.408

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.389

AC:

565279

AN:

1451508

Hom.:

113263

Cov.:

AF XY:

0.390

AC XY:

281644

AN XY:

722602

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.542

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.450

AC:

68269

AN:

151836

Hom.:

16438

Cov.:

AF XY:

0.447

AC XY:

33145

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.430

Hom.:

2618

Bravo

AF:

0.456

Asia WGS

AF:

0.347

AC:

1210

AN:

3478

EpiCase

AF:

0.393

EpiControl

AF:

0.401

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 12, 2019	Variant summary: AKAP9 c.4004_4006dupAAC (p.Lys1335_Leu1336insGln) results in an in-frame insertion that is predicted to insert Gln amino acid into the encoded protein. The variant allele was found at a frequency of 0.4 in 281434 control chromosomes, predominantly at a frequency of 0.63 within the African or African-American subpopulation in the gnomAD database, including 4942 homozygotes. Therefore, suggesting the variant is the major allele observed in population(s) of African-American origin. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant three times a benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign. -
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	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 25, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in dbSNP (all): 865/2184=40% -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2016	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. -

Cardiovascular phenotype

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 17, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 17, 2012	- -

Long QT syndrome 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

- -

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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