NM_005751.5:c.8935C>T

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.8935C>T(p.Pro2979Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,614,044 control chromosomes in the GnomAD database, including 802,048 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 1.0 ( 75657 hom., cov: 29)

Exomes 𝑓: 1.0 ( 726391 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.958

Publications

52 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 links:

CYP51A1 (HGNC:2649): (cytochrome P450 family 51 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

CYP51A1 Gene-Disease associations (from GenCC):

cataract
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

CYP51A1 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 (MetaRNN=9.84979E-7).

BP6

Variant 7-92085597-C-T is Benign according to our data. Variant chr7-92085597-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.8935C>T	p.Pro2979Ser	missense_variant	Exon 36 of 50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.8911C>T	p.Pro2971Ser	missense_variant	Exon 36 of 50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7
AKAP9	NM_001379277.1 link	c.3580C>T	p.Pro1194Ser	missense_variant	Exon 15 of 29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.8935C>T	p.Pro2979Ser	missense_variant	Exon 36 of 50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.997

AC:

151662

AN:

152136

Hom.:

75597

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

0.991

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.996

Gnomad OTH

AF:

0.995

GnomAD2 exomes

AF:

0.996

AC:

250346

AN:

251278

AF XY:

0.996

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.996

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.997

AC:

1457254

AN:

1461790

Hom.:

726391

Cov.:

AF XY:

0.996

AC XY:

724648

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.999

AC:

33460

AN:

33478

American (AMR)

AF:

0.998

AC:

44649

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

26093

AN:

26132

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39692

South Asian (SAS)

AF:

0.992

AC:

85542

AN:

86246

European-Finnish (FIN)

AF:

0.992

AC:

52979

AN:

53406

Middle Eastern (MID)

AF:

0.994

AC:

5732

AN:

5768

European-Non Finnish (NFE)

AF:

0.997

AC:

1108886

AN:

1111956

Other (OTH)

AF:

0.997

AC:

60222

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

232

463

695

926

1158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<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:

0.997

AC:

151781

AN:

152254

Hom.:

75657

Cov.:

AF XY:

0.997

AC XY:

74211

AN XY:

74448

show subpopulations

African (AFR)

AF:

1.00

AC:

41518

AN:

41530

American (AMR)

AF:

0.998

AC:

15259

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.998

AC:

3466

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5192

AN:

5192

South Asian (SAS)

AF:

0.994

AC:

4782

AN:

4812

European-Finnish (FIN)

AF:

0.991

AC:

10519

AN:

10612

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.996

AC:

67738

AN:

68034

Other (OTH)

AF:

0.995

AC:

2101

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.996

Hom.:

155881

Bravo

AF:

0.998

TwinsUK

AF:

0.999

AC:

3703

ALSPAC

AF:

0.998

AC:

3846

ESP6500AA

AF:

1.00

AC:

4405

ESP6500EA

AF:

0.996

AC:

8567

ExAC

AF:

0.996

AC:

120947

Asia WGS

AF:

0.997

AC:

3469

AN:

3478

EpiCase

AF:

0.996

EpiControl

AF:

0.996

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Aug 08, 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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

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

Mar 09, 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

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.2

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.23

.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.081

T;T;T;T

MetaRNN

Benign

9.8e-7

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.96

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

N;.;.;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;.;.;T

Sift4G

Benign

0.89

.;T;.;T

Vest4

0.024

MPC

0.053

ClinPred

0.0014

GERP RS

2.5

Varity_R

0.019

gMVP

0.047

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