Variant chr17-19939814-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_007202.4(AKAP10):c.1221A>G(p.Gln407Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,613,988 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

AKAP10
NM_007202.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.63

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:

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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 (BayesDel_noAF=-0.63).

BP6

Variant 17-19939814-T-C is Benign according to our data. Variant chr17-19939814-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034228.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BS2

High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP10	NM_007202.4 linkuse as main transcript	c.1221A>G	p.Gln407Gln	synonymous_variant	8/15	ENST00000225737.11	NP_009133.2	O43572A0A0S2Z4Z7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKAP10	ENST00000225737.11 linkuse as main transcript	c.1221A>G	p.Gln407Gln	synonymous_variant	8/15	1	NM_007202.4	ENSP00000225737.6	O43572
AKAP10	ENST00000395536.7 linkuse as main transcript	c.1221A>G	p.Gln407Gln	synonymous_variant	8/14	5		ENSP00000378907.3	E7EMD6
AKAP10	ENST00000460046.2 linkuse as main transcript	n.*11A>G		non_coding_transcript_exon_variant	3/4	3		ENSP00000464294.1	J3QRM7
AKAP10	ENST00000460046.2 linkuse as main transcript	n.*11A>G		3_prime_UTR_variant	3/4	3		ENSP00000464294.1	J3QRM7

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000609

AC:

153

AN:

251026

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00397

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000157

AC:

229

AN:

1461702

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000197

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.000348

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AKAP10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2020

This variant is classified as likely 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

-0.63

CADD

Benign

2.8

DANN

Benign

0.36

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