chr17-19909228-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007202.4(AKAP10):c.1936A>G(p.Ile646Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,612,096 control chromosomes in the GnomAD database, including 125,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.43 ( 14762 hom., cov: 33)

Exomes 𝑓: 0.39 ( 111071 hom. )

Consequence

AKAP10
NM_007202.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided U:1B:1

Conservation

PhyloP100: 3.39

Publications

85 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.4074975E-5).

BP6

Variant 17-19909228-T-C is Benign according to our data. Variant chr17-19909228-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 5404.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4 link	c.1936A>G	p.Ile646Val	missense_variant	Exon 14 of 15	ENST00000225737.11	NP_009133.2	O43572A0A0S2Z4Z7
AKAP10	NM_001330152.2 link	c.1762A>G	p.Ile588Val	missense_variant	Exon 13 of 14		NP_001317081.1	E7EMD6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11 link	c.1936A>G	p.Ile646Val	missense_variant	Exon 14 of 15	1	NM_007202.4	ENSP00000225737.6		O43572
AKAP10	ENST00000395536.7 link	c.1762A>G	p.Ile588Val	missense_variant	Exon 13 of 14	5		ENSP00000378907.3		E7EMD6

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64970

AN:

151984

Hom.:

14728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.371

AC:

93016

AN:

250460

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.417

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.385

AC:

562722

AN:

1459994

Hom.:

111071

Cov.:

AF XY:

0.382

AC XY:

277236

AN XY:

726326

show subpopulations

African (AFR)

AF:

0.595

AC:

19869

AN:

33380

American (AMR)

AF:

0.419

AC:

18678

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

9603

AN:

26102

East Asian (EAS)

AF:

0.202

AC:

7994

AN:

39646

South Asian (SAS)

AF:

0.303

AC:

26124

AN:

86086

European-Finnish (FIN)

AF:

0.346

AC:

18423

AN:

53224

Middle Eastern (MID)

AF:

0.407

AC:

2344

AN:

5760

European-Non Finnish (NFE)

AF:

0.393

AC:

436224

AN:

1110922

Other (OTH)

AF:

0.389

AC:

23463

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

16215

32430

48646

64861

81076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13720

27440

41160

54880

68600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.428

AC:

65059

AN:

152102

Hom.:

14762

Cov.:

AF XY:

0.424

AC XY:

31542

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.584

AC:

24218

AN:

41482

American (AMR)

AF:

0.430

AC:

6572

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

1284

AN:

3472

East Asian (EAS)

AF:

0.190

AC:

982

AN:

5166

South Asian (SAS)

AF:

0.287

AC:

1388

AN:

4830

European-Finnish (FIN)

AF:

0.348

AC:

3685

AN:

10590

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25602

AN:

67976

Other (OTH)

AF:

0.415

AC:

876

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1898

3797

5695

7594

9492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.396

Hom.:

47494

Bravo

AF:

0.444

TwinsUK

AF:

0.402

AC:

1490

ALSPAC

AF:

0.406

AC:

1564

ESP6500AA

AF:

0.581

AC:

2560

ESP6500EA

AF:

0.383

AC:

3298

ExAC

AF:

0.373

AC:

45349

Asia WGS

AF:

0.242

AC:

847

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.374

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Reclassified - variant of unknown significance

Uncertain:1

May 15, 2007

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

AKAP10-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.048

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.062

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.000054

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.0

N;.

PhyloP100

3.4

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.12

MPC

0.18

ClinPred

0.0060

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.19

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over