dbSNP rs35359994: AKAP1:p.Gly323Ser (chr17-57106431-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003488.4(AKAP1):c.967G>A(p.Gly323Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,437,222 control chromosomes in the GnomAD database, including 2,678 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 0.061 ( 374 hom., cov: 31)

Exomes 𝑓: 0.033 ( 2304 hom. )

Consequence

AKAP1
NM_003488.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.22

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014906526).

BP6

Variant 17-57106431-G-A is Benign according to our data. Variant chr17-57106431-G-A is described in ClinVar as [Benign]. Clinvar id is 770797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP1	NM_003488.4 link	c.967G>A	p.Gly323Ser	missense_variant	Exon 2 of 11	ENST00000337714.8	NP_003479.1	Q92667-1A0A140VK05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP1	ENST00000337714.8 link	c.967G>A	p.Gly323Ser	missense_variant	Exon 2 of 11	1	NM_003488.4	ENSP00000337736.3		Q92667-1

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

8834

AN:

145222

Hom.:

374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.0633

Gnomad ASJ

AF:

0.0437

Gnomad EAS

AF:

0.00603

Gnomad SAS

AF:

0.0436

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.0455

Gnomad NFE

AF:

0.0858

Gnomad OTH

AF:

0.0668

GnomAD3 exomes

AF:

0.0202

AC:

4643

AN:

230220

Hom.:

269

AF XY:

0.0198

AC XY:

2458

AN XY:

124086

show subpopulations

Gnomad AFR exome

AF:

0.00656

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.00952

Gnomad EAS exome

AF:

0.00306

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0270

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0326

AC:

42173

AN:

1291882

Hom.:

2304

Cov.:

AF XY:

0.0340

AC XY:

21888

AN XY:

644010

show subpopulations

Gnomad4 AFR exome

AF:

0.00906

Gnomad4 AMR exome

AF:

0.0263

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.0136

Gnomad4 SAS exome

AF:

0.0395

Gnomad4 FIN exome

AF:

0.0835

Gnomad4 NFE exome

AF:

0.0309

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0607

AC:

8829

AN:

145340

Hom.:

374

Cov.:

AF XY:

0.0597

AC XY:

4233

AN XY:

70924

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.0632

Gnomad4 ASJ

AF:

0.0437

Gnomad4 EAS

AF:

0.00604

Gnomad4 SAS

AF:

0.0430

Gnomad4 FIN

AF:

0.0818

Gnomad4 NFE

AF:

0.0858

Gnomad4 OTH

AF:

0.0661

Alfa

AF:

0.0902

Hom.:

172

Bravo

AF:

0.0758

TwinsUK

AF:

0.104

AC:

385

ALSPAC

AF:

0.104

AC:

399

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.0706

AC:

607

ExAC

AF:

0.0730

AC:

8826

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.3

DANN

Benign

0.72

DEOGEN2

Benign

0.094

T;T;T;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.63

.;.;T;.;.;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.030

N;.;.;.;N;N

REVEL

Benign

0.014

Sift

Benign

0.21

T;.;.;.;T;T

Sift4G

Benign

0.23

T;T;T;T;T;T

Polyphen

0.023

B;B;B;B;B;.

Vest4

0.029

MPC

0.23

ClinPred

0.0015

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.11

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