Variant 15-85620105-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000394518.7(AKAP13):c.4162-19269A>G variant causes a intron change. The variant allele was found at a frequency of 0.00603 in 1,536,066 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 28 hom. )

Consequence

AKAP13
ENST00000394518.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.79

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:

AKAP13-AS1 (HGNC:):

AKAP13-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009608835).

BP6

Variant 15-85620105-A-G is Benign according to our data. Variant chr15-85620105-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP13	NM_007200.5 linkuse as main transcript	c.4162-19269A>G		intron_variant		ENST00000394518.7	NP_009131.2	Q12802-1
AKAP13	NM_001270546.1 linkuse as main transcript	c.14A>G	p.His5Arg	missense_variant	1/29		NP_001257475.1	Q12802A8MYJ1B0AZU4
AKAP13	NM_006738.6 linkuse as main transcript	c.4162-19269A>G		intron_variant			NP_006729.4	Q12802-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7 linkuse as main transcript	c.4162-19269A>G		intron_variant		1	NM_007200.5	ENSP00000378026.3		Q12802-1

Frequencies

GnomAD3 genomes

AF:

0.00561

AC:

854

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00789

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00491

AC:

660

AN:

134380

Hom.:

AF XY:

0.00482

AC XY:

353

AN XY:

73180

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00352

Gnomad ASJ exome

AF:

0.00639

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.0121

Gnomad NFE exome

AF:

0.00733

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00608

AC:

8412

AN:

1383784

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

4119

AN XY:

682840

show subpopulations

Gnomad4 AFR exome

AF:

0.000855

Gnomad4 AMR exome

AF:

0.00350

Gnomad4 ASJ exome

AF:

0.00755

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.00676

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00560

AC:

853

AN:

152282

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

417

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.00790

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.00473

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00727

AC:

ExAC

AF:

0.00212

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

AKAP13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.013

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0096

T;T

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

1.0

D;D

Sift4G

Benign

0.077

T;T

Vest4

0.60

MVP

0.76

ClinPred

0.13

GERP RS

6.0

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