rs755140795

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005751.5(AKAP9):c.431C>G(p.Ser144Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.43

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10188204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP9	NM_005751.5	MANE Select	c.431C>G	p.Ser144Cys	missense	Exon 5 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.431C>G	p.Ser144Cys	missense	Exon 5 of 50	NP_671714.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.431C>G	p.Ser144Cys	missense	Exon 5 of 50	ENSP00000348573.3
AKAP9	ENST00000394564.5	TSL:1	n.605C>G		non_coding_transcript_exon	Exon 5 of 7
AKAP9	ENST00000359028.7	TSL:5	c.431C>G	p.Ser144Cys	missense	Exon 5 of 51	ENSP00000351922.4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251240

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1111910

Other (OTH)

AF:

0.0000497

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41514

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.026

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

PhyloP100

1.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.3

REVEL

Benign

0.10

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.64

MutPred

0.24

Loss of phosphorylation at S144 (P = 0.0235)

MVP

0.45

MPC

0.34

ClinPred

0.57

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.089

gMVP

0.13

Mutation Taster

=83/17

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over