rs9785013

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005751.5(AKAP9):c.5163-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,570,554 control chromosomes in the GnomAD database, including 128,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16898 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111868 hom. )

Consequence

AKAP9
NM_005751.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.431

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 7-92044988-G-A is Benign according to our data. Variant chr7-92044988-G-A is described in ClinVar as Benign. ClinVar VariationId is 136331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.5163-20G>A		intron_variant	Intron 20 of 49	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.5163-20G>A		intron_variant	Intron 20 of 49		NP_671714.1	Q99996-3Q6PJH3Q5GIA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.5163-20G>A		intron_variant	Intron 20 of 49	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68922

AN:

151872

Hom.:

16861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.452

GnomAD2 exomes

AF:

0.391

AC:

97948

AN:

250218

AF XY:

0.391

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.392

AC:

556095

AN:

1418564

Hom.:

111868

Cov.:

AF XY:

0.392

AC XY:

277698

AN XY:

708534

show subpopulations

African (AFR)

AF:

0.655

AC:

21281

AN:

32504

American (AMR)

AF:

0.323

AC:

14409

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14044

AN:

25882

East Asian (EAS)

AF:

0.205

AC:

8099

AN:

39474

South Asian (SAS)

AF:

0.404

AC:

34487

AN:

85270

European-Finnish (FIN)

AF:

0.387

AC:

20613

AN:

53318

Middle Eastern (MID)

AF:

0.434

AC:

2459

AN:

5660

European-Non Finnish (NFE)

AF:

0.389

AC:

416828

AN:

1072802

Other (OTH)

AF:

0.404

AC:

23875

AN:

59030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

16155

32311

48466

64622

80777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12918

25836

38754

51672

64590

<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:

0.454

AC:

69017

AN:

151990

Hom.:

16898

Cov.:

AF XY:

0.451

AC XY:

33511

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.644

AC:

26713

AN:

41474

American (AMR)

AF:

0.377

AC:

5759

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1889

AN:

3466

East Asian (EAS)

AF:

0.198

AC:

1025

AN:

5180

South Asian (SAS)

AF:

0.402

AC:

1939

AN:

4820

European-Finnish (FIN)

AF:

0.388

AC:

4080

AN:

10526

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26331

AN:

67954

Other (OTH)

AF:

0.451

AC:

951

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1808

3616

5423

7231

9039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.411

Hom.:

20406

Bravo

AF:

0.460

Asia WGS

AF:

0.349

AC:

1216

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jun 08, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 12, 2019

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: AKAP9 c.5163-20G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.39 in 250218 control chromosomes, predominantly at a frequency of 0.65 within the African or African-American subpopulation in the gnomAD database, including 3362 homozygotes. Therefore, suggesting the variant is the major allele observed in population(s) of African-American origin. A ClinVar submission (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 23, 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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Long QT syndrome 11

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.8

(source)

DANN

Benign

0.34

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over