Variant rs11540803 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002605.3(PDE8A):c.163C>G(p.Leu55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,327,742 control chromosomes in the GnomAD database, including 6,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 477 hom., cov: 32)

Exomes 𝑓: 0.094 ( 5560 hom. )

Consequence

PDE8A
NM_002605.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Variant links:

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

PDE8A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014356971).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8A	NM_002605.3 linkuse as main transcript	c.163C>G	p.Leu55Val	missense_variant	1/22	ENST00000394553.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8A	ENST00000394553.6 linkuse as main transcript	c.163C>G	p.Leu55Val	missense_variant	1/22	1	NM_002605.3		O60658-1

Frequencies

GnomAD3 genomes

AF:

0.0658

AC:

9993

AN:

151974

Hom.:

478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.0875

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0580

Gnomad MID

AF:

0.0929

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0766

GnomAD3 exomes

AF:

0.0809

AC:

1137

AN:

14054

Hom.:

AF XY:

0.0877

AC XY:

726

AN XY:

8276

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0688

Gnomad FIN exome

AF:

0.0741

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0648

GnomAD4 exome

AF:

0.0942

AC:

110698

AN:

1175652

Hom.:

5560

Cov.:

AF XY:

0.0940

AC XY:

53365

AN XY:

567984

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.0510

Gnomad4 ASJ exome

AF:

0.0902

Gnomad4 EAS exome

AF:

0.000289

Gnomad4 SAS exome

AF:

0.0729

Gnomad4 FIN exome

AF:

0.0541

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0847

GnomAD4 genome

AF:

0.0657

AC:

9985

AN:

152090

Hom.:

477

Cov.:

AF XY:

0.0630

AC XY:

4686

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.0553

Gnomad4 ASJ

AF:

0.0875

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.0580

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0754

Alfa

AF:

0.0794

Hom.:

Bravo

AF:

0.0634

TwinsUK

AF:

0.0944

AC:

350

ALSPAC

AF:

0.0950

AC:

366

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0709

AC:

331

ExAC

AF:

0.0442

AC:

4047

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.62

Cadd

Benign

2.7

Dann

Benign

0.50

DEOGEN2

Benign

0.064

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.29

T;.;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.010

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.023

MPC

0.19

ClinPred

0.0031

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.040

gMVP

0.098

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over