Variant rs17400325 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_016953.4(PDE11A):c.2180A>G(p.Tyr727Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,602,844 control chromosomes in the GnomAD database, including 1,255 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 89 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1166 hom. )

Consequence

PDE11A
NM_016953.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

PDE11A (HGNC:8773): (phosphodiesterase 11A) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PDE11A links:

PDE11A-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

PDE11A-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0100132525).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4 linkuse as main transcript	c.2180A>G	p.Tyr727Cys	missense_variant	14/20	ENST00000286063.11
PDE11A-AS1	NR_136171.1 linkuse as main transcript	n.339T>C		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11 linkuse as main transcript	c.2180A>G	p.Tyr727Cys	missense_variant	14/20	1	NM_016953.4	P1	Q9HCR9-1
PDE11A-AS1	ENST00000653062.1 linkuse as main transcript	n.509-1303T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4346

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00922

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0368

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0316

AC:

7928

AN:

250840

Hom.:

192

AF XY:

0.0329

AC XY:

4455

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00727

Gnomad AMR exome

AF:

0.0354

Gnomad ASJ exome

AF:

0.0698

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0244

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0456

GnomAD4 exome

AF:

0.0370

AC:

53625

AN:

1450626

Hom.:

1166

Cov.:

AF XY:

0.0371

AC XY:

26780

AN XY:

722492

show subpopulations

Gnomad4 AFR exome

AF:

0.00716

Gnomad4 AMR exome

AF:

0.0367

Gnomad4 ASJ exome

AF:

0.0669

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0242

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0400

Gnomad4 OTH exome

AF:

0.0389

GnomAD4 genome

AF:

0.0285

AC:

4340

AN:

152218

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2081

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00917

Gnomad4 AMR

AF:

0.0452

Gnomad4 ASJ

AF:

0.0689

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.0191

Gnomad4 NFE

AF:

0.0368

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0383

Hom.:

233

Bravo

AF:

0.0304

TwinsUK

AF:

0.0450

AC:

167

ALSPAC

AF:

0.0449

AC:

173

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0403

AC:

347

ExAC

AF:

0.0300

AC:

3643

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0434

EpiControl

AF:

0.0497

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

D;.;.;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

3.7

H;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-8.7

D;D;D;D

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.80

MPC

0.67

ClinPred

0.065

GERP RS

5.7

Varity_R

0.93

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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