Variant 17-57106452-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003488.4(AKAP1):c.988A>G(p.Ser330Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 143,616 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.066 ( 425 hom., cov: 30)

Exomes 𝑓: 0.036 ( 2525 hom. )

Failed GnomAD Quality Control

Consequence

AKAP1
NM_003488.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.98

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015726388).

BP6

Variant 17-57106452-A-G is Benign according to our data. Variant chr17-57106452-A-G is described in ClinVar as [Benign]. Clinvar id is 770798.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP1	NM_003488.4 linkuse as main transcript	c.988A>G	p.Ser330Gly	missense_variant	2/11	ENST00000337714.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP1	ENST00000337714.8 linkuse as main transcript	c.988A>G	p.Ser330Gly	missense_variant	2/11	1	NM_003488.4	P1	Q92667-1

Frequencies

GnomAD3 genomes

AF:

0.0663

AC:

9509

AN:

143500

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.0652

Gnomad ASJ

AF:

0.0483

Gnomad EAS

AF:

0.00628

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.0812

Gnomad MID

AF:

0.0545

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0243

AC:

5610

AN:

230600

Hom.:

257

AF XY:

0.0227

AC XY:

2818

AN XY:

124180

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.0209

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00296

Gnomad SAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.0335

Gnomad NFE exome

AF:

0.0305

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0357

AC:

45761

AN:

1282852

Hom.:

2525

Cov.:

AF XY:

0.0370

AC XY:

23669

AN XY:

640214

show subpopulations

Gnomad4 AFR exome

AF:

0.0593

Gnomad4 AMR exome

AF:

0.0293

Gnomad4 ASJ exome

AF:

0.0352

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.0403

Gnomad4 FIN exome

AF:

0.0882

Gnomad4 NFE exome

AF:

0.0326

Gnomad4 OTH exome

AF:

0.0438

GnomAD4 genome

AF:

0.0662

AC:

9503

AN:

143616

Hom.:

425

Cov.:

AF XY:

0.0645

AC XY:

4511

AN XY:

69940

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.0651

Gnomad4 ASJ

AF:

0.0483

Gnomad4 EAS

AF:

0.00629

Gnomad4 SAS

AF:

0.0415

Gnomad4 FIN

AF:

0.0812

Gnomad4 NFE

AF:

0.0930

Gnomad4 OTH

AF:

0.0677

Alfa

AF:

0.0763

Hom.:

164

TwinsUK

AF:

0.104

AC:

385

ALSPAC

AF:

0.103

AC:

397

ExAC

AF:

0.00475

AC:

569

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.037

DANN

Benign

0.63

DEOGEN2

Benign

0.058

T;T;T;T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;N;N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.42

N;.;.;.;N;N

REVEL

Benign

0.021

Sift

Benign

0.48

T;.;.;.;T;T

Sift4G

Benign

0.48

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;.

Vest4

0.029

MPC

0.22

ClinPred

0.0010

GERP RS

-2.2

Varity_R

0.059

gMVP

0.081

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