Variant chr15-85655524-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007200.5(AKAP13):c.4482C>T(p.Ser1494Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000955 in 1,614,196 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 2 hom. )

Consequence

AKAP13
NM_007200.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.264

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-85655524-C-T is Benign according to our data. Variant chr15-85655524-C-T is described in ClinVar as [Benign]. Clinvar id is 768722.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.264 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP13	NM_007200.5 linkuse as main transcript	c.4482C>T	p.Ser1494Ser	synonymous_variant	11/37	ENST00000394518.7	NP_009131.2	Q12802-1
AKAP13	NM_006738.6 linkuse as main transcript	c.4482C>T	p.Ser1494Ser	synonymous_variant	11/37		NP_006729.4	Q12802-2
AKAP13	NM_001270546.1 linkuse as main transcript	c.402C>T	p.Ser134Ser	synonymous_variant	4/29		NP_001257475.1	Q12802A8MYJ1B0AZU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7 linkuse as main transcript	c.4482C>T	p.Ser1494Ser	synonymous_variant	11/37	1	NM_007200.5	ENSP00000378026.3		Q12802-1

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

520

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00105

AC:

264

AN:

251446

Hom.:

AF XY:

0.000743

AC XY:

101

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000694

AC:

1014

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000616

AC XY:

448

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000429

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00347

AC:

528

AN:

152306

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00382

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.7

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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