Variant rs17761023 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003488.4(AKAP1):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,978 control chromosomes in the GnomAD database, including 8,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.093 ( 766 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7909 hom. )

Consequence

AKAP1
NM_003488.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

AKAP1 (HGNC:367): (A-kinase anchoring protein 1) 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. The encoded protein binds to type I and type II regulatory subunits of PKA and anchors them to the mitochondrion. This protein is speculated to be involved in the cAMP-dependent signal transduction pathway and in directing RNA to a specific cellular compartment. [provided by RefSeq, Jul 2008]

AKAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019706786).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP1	NM_003488.4 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	2/11	ENST00000337714.8	NP_003479.1	Q92667-1A0A140VK05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP1	ENST00000337714.8 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	2/11	1	NM_003488.4	ENSP00000337736.3		Q92667-1

Frequencies

GnomAD3 genomes

AF:

0.0932

AC:

14175

AN:

152018

Hom.:

764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.0886

Gnomad ASJ

AF:

0.0597

Gnomad EAS

AF:

0.00964

Gnomad SAS

AF:

0.0661

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0867

AC:

21801

AN:

251310

Hom.:

1120

AF XY:

0.0883

AC XY:

11996

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.0468

Gnomad ASJ exome

AF:

0.0595

Gnomad EAS exome

AF:

0.00625

Gnomad SAS exome

AF:

0.0716

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0921

GnomAD4 exome

AF:

0.101

AC:

147812

AN:

1461844

Hom.:

7909

Cov.:

AF XY:

0.101

AC XY:

73189

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0678

Gnomad4 AMR exome

AF:

0.0504

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.0154

Gnomad4 SAS exome

AF:

0.0707

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.0906

GnomAD4 genome

AF:

0.0932

AC:

14176

AN:

152134

Hom.:

766

Cov.:

AF XY:

0.0924

AC XY:

6869

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.0885

Gnomad4 ASJ

AF:

0.0597

Gnomad4 EAS

AF:

0.00966

Gnomad4 SAS

AF:

0.0654

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.0999

Alfa

AF:

0.103

Hom.:

1813

Bravo

AF:

0.0904

TwinsUK

AF:

0.108

AC:

399

ALSPAC

AF:

0.105

AC:

405

ESP6500AA

AF:

0.0690

AC:

304

ESP6500EA

AF:

0.102

AC:

879

ExAC

AF:

0.0884

AC:

10734

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;T;T;T;.;.;.;T;T;.;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

T;.;.;T;T;T;T;.;.;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;L;L;L;.;.;.;L;L;.;L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.2

.;N;.;.;.;.;.;.;N;.;D;.

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;D;.;.;.;.;.;.;D;.;D;.

Sift4G

Benign

0.11

T;D;D;D;T;T;T;D;D;T;T;T

Polyphen

0.55

.;P;P;P;.;.;.;P;P;.;.;.

Vest4

0.10, 0.10, 0.10, 0.10, 0.35

MPC

0.33

ClinPred

0.061

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

gMVP

0.83

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over