chr7-92077883-C-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.6945+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,595,566 control chromosomes in the GnomAD database, including 121,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12698 hom., cov: 32)

Exomes 𝑓: 0.38 ( 108785 hom. )

Consequence

AKAP9
NM_005751.5 splice_region, intron

Scores

Splicing: ADA: 0.00004807

Clinical Significance

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

Conservation

PhyloP100: -0.0860

Publications

25 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 7-92077883-C-T is Benign according to our data. Variant chr7-92077883-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKAP9	NM_005751.5	MANE Select	c.6945+8C>T	splice_region intron	N/A	NP_005742.4
AKAP9	NM_147185.3		c.6921+8C>T	splice_region intron	N/A	NP_671714.1
AKAP9	NM_001379277.1		c.1590+8C>T	splice_region intron	N/A	NP_001366206.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKAP9	ENST00000356239.8	TSL:1 MANE Select	c.6945+8C>T	splice_region intron	N/A	ENSP00000348573.3
AKAP9	ENST00000491695.2	TSL:1	c.1590+8C>T	splice_region intron	N/A	ENSP00000494626.2
AKAP9	ENST00000394534.7	TSL:1	c.438+8C>T	splice_region intron	N/A	ENSP00000378042.3

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61256

AN:

151908

Hom.:

12686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.411

GnomAD2 exomes

AF:

0.374

AC:

89691

AN:

240034

AF XY:

0.377

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.385

AC:

555324

AN:

1443542

Hom.:

108785

Cov.:

AF XY:

0.385

AC XY:

276758

AN XY:

718670

show subpopulations

African (AFR)

AF:

0.479

AC:

15774

AN:

32922

American (AMR)

AF:

0.314

AC:

13896

AN:

44212

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14079

AN:

25948

East Asian (EAS)

AF:

0.184

AC:

7238

AN:

39278

South Asian (SAS)

AF:

0.388

AC:

33034

AN:

85078

European-Finnish (FIN)

AF:

0.387

AC:

20256

AN:

52400

Middle Eastern (MID)

AF:

0.428

AC:

2364

AN:

5528

European-Non Finnish (NFE)

AF:

0.387

AC:

425395

AN:

1098426

Other (OTH)

AF:

0.390

AC:

23288

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14276

28552

42827

57103

71379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13298

26596

39894

53192

66490

<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:

0.403

AC:

61313

AN:

152024

Hom.:

12698

Cov.:

AF XY:

0.401

AC XY:

29825

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.472

AC:

19579

AN:

41468

American (AMR)

AF:

0.360

AC:

5491

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1891

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

903

AN:

5168

South Asian (SAS)

AF:

0.387

AC:

1866

AN:

4818

European-Finnish (FIN)

AF:

0.387

AC:

4080

AN:

10540

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26311

AN:

67978

Other (OTH)

AF:

0.410

AC:

866

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1902

3804

5705

7607

9509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.399

Hom.:

12495

Bravo

AF:

0.405

Asia WGS

AF:

0.311

AC:

1080

AN:

3470

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 (6)

Long QT syndrome 11 (2)

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

-0.71

CADD

Benign

3.8

(source)

DANN

Benign

0.59

PhyloP100

-0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0060

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