Variant 17-57106116-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000337714.8(AKAP1):c.652G>A(p.Ala218Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 1,606,984 control chromosomes in the GnomAD database, including 65 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 0.0086 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 59 hom. )

Consequence

AKAP1
ENST00000337714.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.39

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032155812).

BP6

Variant 17-57106116-G-A is Benign according to our data. Variant chr17-57106116-G-A is described in ClinVar as [Benign]. Clinvar id is 777890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1304 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP1	NM_003488.4 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	2/11	ENST00000337714.8	NP_003479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP1	ENST00000337714.8 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	2/11	1	NM_003488.4	ENSP00000337736	P1	Q92667-1

Frequencies

GnomAD3 genomes

AF:

0.00853

AC:

1299

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00805

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00706

AC:

1743

AN:

246838

Hom.:

AF XY:

0.00702

AC XY:

936

AN XY:

133328

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00473

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00880

Gnomad OTH exome

AF:

0.00985

GnomAD4 exome

AF:

0.00873

AC:

12699

AN:

1454646

Hom.:

Cov.:

AF XY:

0.00864

AC XY:

6245

AN XY:

722714

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00496

Gnomad4 FIN exome

AF:

0.00179

Gnomad4 NFE exome

AF:

0.00935

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00856

AC:

1304

AN:

152338

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00806

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00845

Hom.:

Bravo

AF:

0.00920

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00710

AC:

862

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.069

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

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.69

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

MetaRNN

Benign

0.0032

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.38

N;.;.;.;N;N;.

REVEL

Benign

0.082

Sift

Benign

0.096

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

Sift4G

Benign

0.75

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

Polyphen

0.0

B;B;B;B;B;.;.

Vest4

0.023

MVP

0.27

MPC

0.23

ClinPred

0.010

GERP RS

4.5

Varity_R

0.038

gMVP

0.26

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