Genetic Variant PDE3A:c.960+42782T>C (chr12-20413026-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000921.5(PDE3A):c.960+42782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,112 control chromosomes in the GnomAD database, including 30,797 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 0.62 ( 30797 hom., cov: 33)

Consequence

PDE3A
NM_000921.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.578

Publications

7 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 Gene-Disease associations (from GenCC):

brachydactyly-arterial hypertension syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

PDE3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5 link	c.960+42782T>C	intron_variant	Intron 1 of 15	ENST00000359062.4	NP_000912.3	Q14432
PDE3A	NM_001378407.1 link	c.960+42782T>C	intron_variant	Intron 1 of 13		NP_001365336.1
PDE3A	NM_001378408.1 link	c.-69+42782T>C	intron_variant	Intron 1 of 17		NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4 link	c.960+42782T>C		intron_variant	Intron 1 of 15	1	NM_000921.5	ENSP00000351957.3		Q14432
PDE3A	ENST00000542675.1 link	n.120+42782T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93911

AN:

151994

Hom.:

30785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.618

AC:

93960

AN:

152112

Hom.:

30797

Cov.:

AF XY:

0.627

AC XY:

46601

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.382

AC:

15846

AN:

41480

American (AMR)

AF:

0.687

AC:

10493

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2103

AN:

3464

East Asian (EAS)

AF:

0.885

AC:

4573

AN:

5170

South Asian (SAS)

AF:

0.709

AC:

3420

AN:

4824

European-Finnish (FIN)

AF:

0.805

AC:

8525

AN:

10588

Middle Eastern (MID)

AF:

0.606

AC:

177

AN:

292

European-Non Finnish (NFE)

AF:

0.688

AC:

46815

AN:

68002

Other (OTH)

AF:

0.600

AC:

1268

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1711

3422

5132

6843

8554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.658

Hom.:

104274

Bravo

AF:

0.599

Asia WGS

AF:

0.770

AC:

2677

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.9

(source)

DANN

Benign

0.71

PhyloP100

0.58

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over