12-20369318-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5 link	c.34G>A	p.Asp12Asn	missense_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3	Q14432
PDE3A	NM_001378407.1 link	c.34G>A	p.Asp12Asn	missense_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1 link	c.-995G>A		5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1 link	n.416+523C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4 link	c.34G>A	p.Asp12Asn	missense_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3		Q14432
PDE3A-AS1	ENST00000535755.1 link	n.422+523C>T		intron_variant	Intron 1 of 1	4

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

GnomAD3 exomes

AF:

0.287

AC:

40744

AN:

142038

Hom.:

6322

AF XY:

0.288

AC XY:

21920

AN XY:

76074

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 SAS exome

AF:

0.270

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

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.344

AC:

52233

AN:

151990

Hom.:

9574

Cov.:

AF XY:

0.343

AC XY:

25444

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.348

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.301

Hom.:

14735

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

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

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

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

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