7-92002992-C-T

Position:

chr7-92002992-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.3075C>T(p.Thr1025Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,613,322 control chromosomes in the GnomAD database, including 617,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61977 hom., cov: 32)

Exomes 𝑓: 0.87 ( 555670 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.954

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:

AKAP9 (HGNC:):

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=-0.87).

BP6

Variant 7-92002992-C-T is Benign according to our data. Variant chr7-92002992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92002992-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.954 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 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.3075C>T	p.Thr1025Thr	synonymous_variant	8/50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 linkuse as main transcript	c.3075C>T	p.Thr1025Thr	synonymous_variant	8/50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.3075C>T	p.Thr1025Thr	synonymous_variant	8/50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.901

AC:

136947

AN:

152002

Hom.:

61915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.974

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.902

GnomAD3 exomes

AF:

0.893

AC:

224068

AN:

250870

Hom.:

100344

AF XY:

0.890

AC XY:

120758

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.942

Gnomad ASJ exome

AF:

0.883

Gnomad EAS exome

AF:

0.973

Gnomad SAS exome

AF:

0.894

Gnomad FIN exome

AF:

0.846

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.872

AC:

1273460

AN:

1461202

Hom.:

555670

Cov.:

AF XY:

0.871

AC XY:

633293

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.977

Gnomad4 AMR exome

AF:

0.939

Gnomad4 ASJ exome

AF:

0.885

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.896

Gnomad4 FIN exome

AF:

0.841

Gnomad4 NFE exome

AF:

0.861

Gnomad4 OTH exome

AF:

0.874

GnomAD4 genome

AF:

0.901

AC:

137069

AN:

152120

Hom.:

61977

Cov.:

AF XY:

0.902

AC XY:

67061

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.974

Gnomad4 AMR

AF:

0.921

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.971

Gnomad4 SAS

AF:

0.893

Gnomad4 FIN

AF:

0.847

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.901

Alfa

AF:

0.878

Hom.:

60887

Bravo

AF:

0.911

Asia WGS

AF:

0.906

AC:

3150

AN:

3478

EpiCase

AF:

0.863

EpiControl

AF:

0.864

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	PreventionGenetics, part of Exact Sciences	-	- -
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	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 09, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 04, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Long QT syndrome 11

Benign:2

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

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

Mar 09, 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

-0.87

CADD

Benign

0.15

DANN

Benign

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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