rs12305038

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000921.5(PDE3A):c.34G>A(p.Asp12Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,544,406 control chromosomes in the GnomAD database, including 74,230 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 Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9574 hom., cov: 32)

Exomes 𝑓: 0.30 ( 64656 hom. )

Consequence

PDE3A
NM_000921.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.45

Publications

30 publications found

Variant links:

Genes affected

PDE3A (HGNC:8778): (phosphodiesterase 3A) This gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

PDE3A links:

PDE3A-AS1 (HGNC:40436): (PDE3A antisense RNA 1)

PDE3A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5376678E-4).

BP6

Variant 12-20369318-G-A is Benign according to our data. Variant chr12-20369318-G-A is described in ClinVar as Benign. ClinVar VariationId is 1221712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDE3A	NM_000921.5	MANE Select	c.34G>A	p.Asp12Asn	missense	Exon 1 of 16	NP_000912.3
PDE3A	NM_001378407.1		c.34G>A	p.Asp12Asn	missense	Exon 1 of 14	NP_001365336.1
PDE3A	NM_001378408.1		c.-995G>A		5_prime_UTR	Exon 1 of 18	NP_001365337.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.34G>A	p.Asp12Asn	missense	Exon 1 of 16	ENSP00000351957.3	Q14432
PDE3A	ENST00000951762.1		c.34G>A	p.Asp12Asn	missense	Exon 1 of 15	ENSP00000621821.1
PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+523C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52207

AN:

151872

Hom.:

9567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.287

AC:

40744

AN:

142038

AF XY:

0.288

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.301

AC:

419779

AN:

1392416

Hom.:

64656

Cov.:

AF XY:

0.300

AC XY:

206105

AN XY:

686078

show subpopulations

African (AFR)

AF:

0.480

AC:

15090

AN:

31450

American (AMR)

AF:

0.165

AC:

5863

AN:

35462

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

8341

AN:

24826

East Asian (EAS)

AF:

0.288

AC:

10247

AN:

35634

South Asian (SAS)

AF:

0.270

AC:

21232

AN:

78548

European-Finnish (FIN)

AF:

0.349

AC:

16632

AN:

47654

Middle Eastern (MID)

AF:

0.230

AC:

1205

AN:

5228

European-Non Finnish (NFE)

AF:

0.301

AC:

323702

AN:

1075944

Other (OTH)

AF:

0.303

AC:

17467

AN:

57670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

15961

31922

47882

63843

79804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10878

21756

32634

43512

54390

<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:

0.344

AC:

52233

AN:

151990

Hom.:

9574

Cov.:

AF XY:

0.343

AC XY:

25444

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.472

AC:

19576

AN:

41498

American (AMR)

AF:

0.222

AC:

3391

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1165

AN:

3470

East Asian (EAS)

AF:

0.295

AC:

1497

AN:

5066

South Asian (SAS)

AF:

0.261

AC:

1260

AN:

4828

European-Finnish (FIN)

AF:

0.348

AC:

3682

AN:

10584

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20710

AN:

67928

Other (OTH)

AF:

0.310

AC:

657

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1735

3470

5204

6939

8674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.309

Hom.:

24143

Bravo

AF:

0.338

TwinsUK

AF:

0.291

AC:

1079

ALSPAC

AF:

0.315

AC:

1215

ESP6500AA

AF:

0.416

AC:

1554

ESP6500EA

AF:

0.269

AC:

1943

ExAC

AF:

0.174

AC:

10458

Asia WGS

AF:

0.291

AC:

1017

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.61

MetaRNN

Benign

0.00025

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

2.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.010

REVEL

Benign

0.18

Sift

Benign

0.21

Sift4G

Benign

0.42

Polyphen

0.079

Vest4

0.083

MPC

0.85

ClinPred

0.019

GERP RS

3.9

Varity_R

0.080

gMVP

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over