dbSNP rs745191: AKAP13:p.Gly624Val (chr15-85579939-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007200.5(AKAP13):c.1871G>T(p.Gly624Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,956 control chromosomes in the GnomAD database, including 55,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 4148 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51173 hom. )

Consequence

AKAP13
NM_007200.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Variant links:

Genes affected

AKAP13 (HGNC:371): (A-kinase anchoring protein 13) 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. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]

AKAP13 links:

ENSG00000259375 (HGNC:):

ENSG00000259375 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003947228).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP13	NM_007200.5 link	c.1871G>T	p.Gly624Val	missense_variant	Exon 7 of 37	ENST00000394518.7	NP_009131.2	Q12802-1
AKAP13	NM_006738.6 link	c.1871G>T	p.Gly624Val	missense_variant	Exon 7 of 37		NP_006729.4	Q12802-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKAP13	ENST00000394518.7 link	c.1871G>T	p.Gly624Val	missense_variant	Exon 7 of 37	1	NM_007200.5	ENSP00000378026.3	Q12802-1
AKAP13	ENST00000361243.6 link	c.1871G>T	p.Gly624Val	missense_variant	Exon 7 of 37	1		ENSP00000354718.2	Q12802-2
AKAP13	ENST00000559362.5 link	c.1871G>T	p.Gly624Val	missense_variant	Exon 7 of 15	2		ENSP00000453768.1	H0YMW2
ENSG00000259375	ENST00000561409.1 link	n.159+81C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30878

AN:

152004

Hom.:

4152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0479

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.228

AC:

57291

AN:

250856

Hom.:

7851

AF XY:

0.237

AC XY:

32111

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.0269

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.256

AC:

373697

AN:

1461834

Hom.:

51173

Cov.:

AF XY:

0.256

AC XY:

186140

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0434

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.0208

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.203

AC:

30875

AN:

152122

Hom.:

4148

Cov.:

AF XY:

0.200

AC XY:

14875

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.279

Hom.:

14584

Bravo

AF:

0.195

TwinsUK

AF:

0.259

AC:

962

ALSPAC

AF:

0.270

AC:

1040

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.284

AC:

2442

ExAC

AF:

0.228

AC:

27629

Asia WGS

AF:

0.102

AC:

354

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.9

DANN

Benign

0.94

DEOGEN2

Benign

0.026

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

.;L;L

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.049

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.15

T;D;D

Polyphen

0.0010

.;B;B

Vest4

0.12, 0.083

MPC

0.19

ClinPred

0.023

GERP RS

0.36

Varity_R

0.17

gMVP

0.24

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