chr7-92012614-A-G

Variant names:

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.3504A>G(p.Glu1168Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,610,690 control chromosomes in the GnomAD database, including 124,580 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 ( 13552 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111028 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.553

Publications

30 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 7-92012614-A-G is Benign according to our data. Variant chr7-92012614-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.553 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

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.3504A>G	p.Glu1168Glu	synonymous	Exon 9 of 50	NP_005742.4
	AKAP9	NM_147185.3		c.3504A>G	p.Glu1168Glu	synonymous	Exon 9 of 50	NP_671714.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.3504A>G	p.Glu1168Glu	synonymous	Exon 9 of 50	ENSP00000348573.3
AKAP9	ENST00000359028.7	TSL:5	c.3504A>G	p.Glu1168Glu	synonymous	Exon 9 of 51	ENSP00000351922.4
AKAP9	ENST00000681412.1		c.3504A>G	p.Glu1168Glu	synonymous	Exon 9 of 49	ENSP00000506486.1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63001

AN:

151858

Hom.:

13534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.422

GnomAD2 exomes

AF:

0.379

AC:

95091

AN:

251022

AF XY:

0.380

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.311

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:

563835

AN:

1458712

Hom.:

111028

Cov.:

AF XY:

0.387

AC XY:

280680

AN XY:

725836

show subpopulations

African (AFR)

AF:

0.518

AC:

17310

AN:

33386

American (AMR)

AF:

0.316

AC:

14131

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14172

AN:

26116

East Asian (EAS)

AF:

0.185

AC:

7311

AN:

39620

South Asian (SAS)

AF:

0.389

AC:

33523

AN:

86080

European-Finnish (FIN)

AF:

0.387

AC:

20639

AN:

53364

Middle Eastern (MID)

AF:

0.427

AC:

2457

AN:

5752

European-Non Finnish (NFE)

AF:

0.388

AC:

430634

AN:

1109422

Other (OTH)

AF:

0.392

AC:

23658

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16233

32466

48700

64933

81166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13480

26960

40440

53920

67400

<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:

0.415

AC:

63071

AN:

151978

Hom.:

13552

Cov.:

AF XY:

0.412

AC XY:

30602

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.514

AC:

21296

AN:

41410

American (AMR)

AF:

0.361

AC:

5517

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1889

AN:

3468

East Asian (EAS)

AF:

0.173

AC:

897

AN:

5180

South Asian (SAS)

AF:

0.387

AC:

1863

AN:

4816

European-Finnish (FIN)

AF:

0.386

AC:

4074

AN:

10546

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26317

AN:

67964

Other (OTH)

AF:

0.422

AC:

890

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1845

3690

5535

7380

9225

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:

0.403

Hom.:

41380

Bravo

AF:

0.417

Asia WGS

AF:

0.314

AC:

1094

AN:

3476

EpiCase

AF:

0.393

EpiControl

AF:

0.403

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Long QT syndrome 11 (2)

Cardiovascular phenotype (1)

Congenital long QT syndrome (1)

Long QT syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.7

(source)

DANN

Benign

0.54

PhyloP100

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over