Variant 17-19931799-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007202.4(AKAP10):c.1641+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,611,352 control chromosomes in the GnomAD database, including 11,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.095 ( 788 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11164 hom. )

Consequence

AKAP10
NM_007202.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002518

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-19931799-C-T is Benign according to our data. Variant chr17-19931799-C-T is described in ClinVar as [Benign]. Clinvar id is 3055540.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AKAP10	NM_007202.4 linkuse as main transcript	c.1641+6G>A	splice_donor_region_variant, intron_variant	ENST00000225737.11
AKAP10	NM_001330152.2 linkuse as main transcript	c.1467+4487G>A	intron_variant
AKAP10	XR_007065258.1 linkuse as main transcript	n.1790+6G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
AKAP10	ENST00000225737.11 linkuse as main transcript	c.1641+6G>A	splice_donor_region_variant, intron_variant	1	NM_007202.4	P1
AKAP10	ENST00000395536.7 linkuse as main transcript	c.1467+4487G>A	intron_variant	5
AKAP10	ENST00000583951.1 linkuse as main transcript	c.62+6G>A	splice_donor_region_variant, intron_variant	3
AKAP10	ENST00000578898.1 linkuse as main transcript	c.73+6G>A	splice_donor_region_variant, intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0948

AC:

14407

AN:

152008

Hom.:

784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0803

Gnomad SAS

AF:

0.0849

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0819

GnomAD3 exomes

AF:

0.106

AC:

26466

AN:

248790

Hom.:

1570

AF XY:

0.106

AC XY:

14212

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.0822

Gnomad EAS exome

AF:

0.0792

Gnomad SAS exome

AF:

0.0831

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.121

AC:

176387

AN:

1459228

Hom.:

11164

Cov.:

AF XY:

0.119

AC XY:

86654

AN XY:

725778

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.0810

Gnomad4 EAS exome

AF:

0.0912

Gnomad4 SAS exome

AF:

0.0819

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0948

AC:

14420

AN:

152124

Hom.:

788

Cov.:

AF XY:

0.0943

AC XY:

7011

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0376

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.0805

Gnomad4 SAS

AF:

0.0849

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.0839

Alfa

AF:

0.109

Hom.:

464

Bravo

AF:

0.0901

Asia WGS

AF:

0.0710

AC:

248

AN:

3478

EpiCase

AF:

0.113

EpiControl

AF:

0.111

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AKAP10-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.21

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00025

dbscSNV1_RF

Benign

0.010

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