7-92062287-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005751.5(AKAP9):c.5778C>T(p.Gly1926Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,607,738 control chromosomes in the GnomAD database, including 122,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12492 hom., cov: 32)

Exomes 𝑓: 0.38 ( 110007 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.273

Publications

24 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-92062287-C-T is Benign according to our data. Variant chr7-92062287-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.273 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.5778C>T	p.Gly1926Gly	synonymous_variant	Exon 24 of 50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.5778C>T	p.Gly1926Gly	synonymous_variant	Exon 24 of 50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7
AKAP9	NM_001379277.1 link	c.423C>T	p.Gly141Gly	synonymous_variant	Exon 3 of 29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.5778C>T	p.Gly1926Gly	synonymous_variant	Exon 24 of 50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60817

AN:

151770

Hom.:

12480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.410

GnomAD2 exomes

AF:

0.375

AC:

94000

AN:

250612

AF XY:

0.378

show subpopulations

Gnomad AFR exome

AF:

0.470

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.385

AC:

560291

AN:

1455850

Hom.:

110007

Cov.:

AF XY:

0.385

AC XY:

279161

AN XY:

724590

show subpopulations

African (AFR)

AF:

0.471

AC:

15693

AN:

33318

American (AMR)

AF:

0.314

AC:

14034

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

14148

AN:

26086

East Asian (EAS)

AF:

0.184

AC:

7311

AN:

39638

South Asian (SAS)

AF:

0.389

AC:

33513

AN:

86094

European-Finnish (FIN)

AF:

0.387

AC:

20649

AN:

53396

Middle Eastern (MID)

AF:

0.426

AC:

2446

AN:

5746

European-Non Finnish (NFE)

AF:

0.388

AC:

429058

AN:

1106706

Other (OTH)

AF:

0.389

AC:

23439

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

16333

32666

49000

65333

81666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13398

26796

40194

53592

66990

<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:

0.401

AC:

60875

AN:

151888

Hom.:

12492

Cov.:

AF XY:

0.399

AC XY:

29605

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.464

AC:

19221

AN:

41400

American (AMR)

AF:

0.357

AC:

5450

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1891

AN:

3472

East Asian (EAS)

AF:

0.174

AC:

902

AN:

5172

South Asian (SAS)

AF:

0.387

AC:

1868

AN:

4824

European-Finnish (FIN)

AF:

0.387

AC:

4076

AN:

10534

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26279

AN:

67920

Other (OTH)

AF:

0.408

AC:

861

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1890

3780

5671

7561

9451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.400

Hom.:

22901

Bravo

AF:

0.402

Asia WGS

AF:

0.311

AC:

1084

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 09, 2019

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 10, 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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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: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 18, 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

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.4

(source)

DANN

Benign

0.66

PhyloP100

0.27

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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