rs9785013

Positions:

chr7-92044988-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000356239.8(AKAP9):c.5163-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,570,554 control chromosomes in the GnomAD database, including 128,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16898 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111868 hom. )

Consequence

AKAP9
ENST00000356239.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.431

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 7-92044988-G-A is Benign according to our data. Variant chr7-92044988-G-A is described in ClinVar as [Benign]. Clinvar id is 136331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92044988-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP9	NM_005751.5 linkuse as main transcript	c.5163-20G>A		intron_variant		ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3 linkuse as main transcript	c.5163-20G>A		intron_variant			NP_671714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.5163-20G>A		intron_variant		1	NM_005751.5	ENSP00000348573	P4	Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68922

AN:

151872

Hom.:

16861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.452

GnomAD3 exomes

AF:

0.391

AC:

97948

AN:

250218

Hom.:

20351

AF XY:

0.391

AC XY:

52930

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.408

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.392

AC:

556095

AN:

1418564

Hom.:

111868

Cov.:

AF XY:

0.392

AC XY:

277698

AN XY:

708534

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.454

AC:

69017

AN:

151990

Hom.:

16898

Cov.:

AF XY:

0.451

AC XY:

33511

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.412

Hom.:

15140

Bravo

AF:

0.460

Asia WGS

AF:

0.349

AC:

1216

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 12, 2019	Variant summary: AKAP9 c.5163-20G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.39 in 250218 control chromosomes, predominantly at a frequency of 0.65 within the African or African-American subpopulation in the gnomAD database, including 3362 homozygotes. Therefore, suggesting the variant is the major allele observed in population(s) of African-American origin. A ClinVar submission (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2011	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Long QT syndrome 11

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.8

DANN

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over