NM_005751.5:c.9145C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005751.5(AKAP9):c.9145C>T(p.Leu3049Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,612,624 control chromosomes in the GnomAD database, including 116,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9216 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106861 hom. )

Consequence

AKAP9
NM_005751.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-92086348-C-T is Benign according to our data. Variant chr7-92086348-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92086348-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP9	NM_005751.5 link	c.9145C>T	p.Leu3049Leu	synonymous_variant	Exon 37 of 50	ENST00000356239.8	NP_005742.4	Q99996-2Q6PJH3Q5GIA7
AKAP9	NM_147185.3 link	c.9121C>T	p.Leu3041Leu	synonymous_variant	Exon 37 of 50		NP_671714.1	Q99996-3Q6PJH3Q5GIA7
AKAP9	NM_001379277.1 link	c.3790C>T	p.Leu1264Leu	synonymous_variant	Exon 16 of 29		NP_001366206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP9	ENST00000356239.8 link	c.9145C>T	p.Leu3049Leu	synonymous_variant	Exon 37 of 50	1	NM_005751.5	ENSP00000348573.3		Q99996-2

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51516

AN:

151734

Hom.:

9219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.359

AC:

90129

AN:

251322

Hom.:

16961

AF XY:

0.365

AC XY:

49641

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.546

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.379

AC:

553345

AN:

1460774

Hom.:

106861

Cov.:

AF XY:

0.380

AC XY:

276170

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.339

AC:

51524

AN:

151850

Hom.:

9216

Cov.:

AF XY:

0.339

AC XY:

25164

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.383

Hom.:

14267

Bravo

AF:

0.331

Asia WGS

AF:

0.294

AC:

1026

AN:

3478

EpiCase

AF:

0.391

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

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 10, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 4626/13006=35% -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 09, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome 11

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 18, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.38

CADD

Benign

7.9

DANN

Benign

0.86

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