rs1063243

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005751.5(AKAP9):c.10426A>C(p.Arg3476Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,613,192 control chromosomes in the GnomAD database, including 125,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13845 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111551 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.907

Publications

34 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 7-92097613-A-C is Benign according to our data. Variant chr7-92097613-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.907 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.10426A>C	p.Arg3476Arg	synonymous_variant	Exon 42 of 50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.10402A>C	p.Arg3468Arg	synonymous_variant	Exon 42 of 50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7
AKAP9	NM_001379277.1 link	c.5071A>C	p.Arg1691Arg	synonymous_variant	Exon 21 of 29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.10426A>C	p.Arg3476Arg	synonymous_variant	Exon 42 of 50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63548

AN:

151976

Hom.:

13826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.425

GnomAD2 exomes

AF:

0.380

AC:

95376

AN:

251212

AF XY:

0.381

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.312

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:

0.394

GnomAD4 exome

AF:

0.387

AC:

565882

AN:

1461098

Hom.:

111551

Cov.:

AF XY:

0.387

AC XY:

281564

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.531

AC:

17770

AN:

33462

American (AMR)

AF:

0.317

AC:

14171

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14181

AN:

26134

East Asian (EAS)

AF:

0.185

AC:

7328

AN:

39686

South Asian (SAS)

AF:

0.390

AC:

33598

AN:

86204

European-Finnish (FIN)

AF:

0.387

AC:

20656

AN:

53414

Middle Eastern (MID)

AF:

0.426

AC:

2284

AN:

5358

European-Non Finnish (NFE)

AF:

0.389

AC:

432131

AN:

1111766

Other (OTH)

AF:

0.394

AC:

23763

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19809

39618

59428

79237

99046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13546

27092

40638

54184

67730

<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:

0.418

AC:

63619

AN:

152094

Hom.:

13845

Cov.:

AF XY:

0.415

AC XY:

30875

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.525

AC:

21791

AN:

41468

American (AMR)

AF:

0.363

AC:

5548

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1890

AN:

3472

East Asian (EAS)

AF:

0.174

AC:

899

AN:

5180

South Asian (SAS)

AF:

0.387

AC:

1865

AN:

4818

European-Finnish (FIN)

AF:

0.385

AC:

4067

AN:

10564

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26335

AN:

67996

Other (OTH)

AF:

0.425

AC:

898

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1879

3757

5636

7514

9393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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.:

44605

Bravo

AF:

0.422

Asia WGS

AF:

0.316

AC:

1102

AN:

3478

EpiCase

AF:

0.393

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

PreventionGenetics, part of Exact Sciences

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. -

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

- -

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: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

-0.75

CADD

Benign

8.9

(source)

DANN

Benign

0.53

PhyloP100

0.91

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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