Variant chr17-19931878-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007202.4(AKAP10):c.1568C>T(p.Ser523Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00328 in 1,614,032 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 96 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 83 hom. )

Consequence

AKAP10
NM_007202.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.97

Variant links:

Genes affected

AKAP10 (HGNC:368): (A-kinase anchoring protein 10) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

AKAP10 links:

AKAP10 (HGNC:):

AKAP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031231642).

BP6

Variant 17-19931878-G-A is Benign according to our data. Variant chr17-19931878-G-A is described in ClinVar as [Benign]. Clinvar id is 3041825.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP10	NM_007202.4 linkuse as main transcript	c.1568C>T	p.Ser523Leu	missense_variant	10/15	ENST00000225737.11	NP_009133.2	O43572A0A0S2Z4Z7
AKAP10	NM_001330152.2 linkuse as main transcript	c.1467+4408C>T		intron_variant			NP_001317081.1	E7EMD6
AKAP10	XR_007065258.1 linkuse as main transcript	n.1717C>T		non_coding_transcript_exon_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKAP10	ENST00000225737.11 linkuse as main transcript	c.1568C>T	p.Ser523Leu	missense_variant	10/15	1	NM_007202.4	ENSP00000225737.6	O43572
AKAP10	ENST00000395536.7 linkuse as main transcript	c.1467+4408C>T		intron_variant		5		ENSP00000378907.3	E7EMD6
AKAP10	ENST00000583951.1 linkuse as main transcript	c.-12C>T		upstream_gene_variant		3		ENSP00000463398.1	J3QL61
AKAP10	ENST00000578898.1 linkuse as main transcript	n.-2C>T		upstream_gene_variant		3		ENSP00000466329.1	K7EM25

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2741

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00446

AC:

1121

AN:

251364

Hom.:

AF XY:

0.00330

AC XY:

448

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0629

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00175

AC:

2558

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1101

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000764

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.0180

AC:

2744

AN:

152168

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1264

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0634

Gnomad4 AMR

AF:

0.00472

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.0202

ESP6500AA

AF:

0.0672

AC:

296

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00577

AC:

700

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AKAP10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.0

REVEL

Benign

0.089

Sift

Benign

0.10

Sift4G

Benign

0.33

Polyphen

0.0010

Vest4

0.11

MVP

0.16

MPC

0.19

ClinPred

0.0087

GERP RS

4.9

Varity_R

0.057

gMVP

0.32

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