rs142729919

Positions:

chr7-92099831-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005751.5(AKAP9):c.10858A>G(p.Ile3620Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,614,052 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

AKAP9
NM_005751.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.399

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:

CYP51A1 (HGNC:2649): (cytochrome P450 family 51 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

CYP51A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 7-92099831-A-G is Benign according to our data. Variant chr7-92099831-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 191557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92099831-A-G is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 421 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKAP9	NM_005751.5 linkuse as main transcript	c.10858A>G	p.Ile3620Val	missense_variant	44/50	ENST00000356239.8	NP_005742.4
AKAP9	NM_147185.3 linkuse as main transcript	c.10834A>G	p.Ile3612Val	missense_variant	44/50		NP_671714.1
AKAP9	NM_001379277.1 linkuse as main transcript	c.5503A>G	p.Ile1835Val	missense_variant	23/29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 linkuse as main transcript	c.10858A>G	p.Ile3620Val	missense_variant	44/50	1	NM_005751.5	ENSP00000348573	P4	Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000744

AC:

187

AN:

251354

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000295

AC:

431

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

181

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.00277

AC:

421

AN:

152256

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00980

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000426

Hom.:

Bravo

AF:

0.00294

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000931

AC:

113

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jun 24, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 15, 2022	- -

Long QT syndrome 11

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 17, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Jan 23, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2018

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.27

.;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.58

N;.;N

REVEL

Benign

0.054

Sift

Benign

0.28

T;.;T

Sift4G

Benign

0.47

.;.;T

Vest4

0.21

MVP

0.11

MPC

0.047

ClinPred

0.010

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.77

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.77

Position offset: -1

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