rs10228334

Positions:

chr7-92084658-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005751.5(AKAP9):c.8665C>T(p.Leu2889=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,603,034 control chromosomes in the GnomAD database, including 123,832 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 ( 13549 hom., cov: 32)

Exomes 𝑓: 0.39 ( 110283 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0130

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-92084658-C-T is Benign according to our data. Variant chr7-92084658-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92084658-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKAP9	NM_005751.5 linkuse as main transcript	c.8665C>T	p.Leu2889=	synonymous_variant	34/50	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3 linkuse as main transcript	c.8641C>T	p.Leu2881=	synonymous_variant	34/50		NP_671714.1
AKAP9	NM_001379277.1 linkuse as main transcript	c.3310C>T	p.Leu1104=	synonymous_variant	13/29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.8665C>T	p.Leu2889=	synonymous_variant	34/50	1	NM_005751.5	ENSP00000348573	P4	Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63008

AN:

151840

Hom.:

13531

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:

0.174

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.378

AC:

94441

AN:

250064

Hom.:

18697

AF XY:

0.379

AC XY:

51352

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.385

AC:

559267

AN:

1451076

Hom.:

110283

Cov.:

AF XY:

0.386

AC XY:

278704

AN XY:

722482

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.542

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.415

AC:

63078

AN:

151958

Hom.:

13549

Cov.:

AF XY:

0.412

AC XY:

30610

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.403

Hom.:

15544

Bravo

AF:

0.417

Asia WGS

AF:

0.313

AC:

1086

AN:

3466

EpiCase

AF:

0.392

EpiControl

AF:

0.402

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 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, 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 09, 2019	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2015	- -

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

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2015

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

-0.88

CADD

Benign

0.88

DANN

Benign

0.44

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