Genetic Variant PDE3A:c.-77_-74delTGTG (chr12-20369190-CGTGT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000921.5(PDE3A):c.-77_-74delTGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 649,772 control chromosomes in the GnomAD database, including 19,981 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 9562 hom., cov: 0)

Exomes 𝑓: 0.28 ( 10419 hom. )

Consequence

PDE3A
NM_000921.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.962

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 -10 ACMG points.

BP6

Variant 12-20369190-CGTGT-C is Benign according to our data. Variant chr12-20369190-CGTGT-C is described in ClinVar as [Benign]. Clinvar id is 1241874.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5 link	c.-77_-74delTGTG	5_prime_UTR_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3	Q14432
PDE3A	NM_001378407.1 link	c.-77_-74delTGTG	5_prime_UTR_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1 link	c.-1105_-1102delTGTG	5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1 link	n.416+647_416+650delACAC	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062 link	c.-77_-74delTGTG		5_prime_UTR_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3		Q14432
PDE3A-AS1	ENST00000535755.1 link	n.422+647_422+650delACAC		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

51693

AN:

145282

Hom.:

9551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.278

AC:

140326

AN:

504382

Hom.:

10419

AF XY:

0.277

AC XY:

71575

AN XY:

258254

show subpopulations

Gnomad4 AFR exome

AF:

0.422

AC:

5274

AN:

12512

Gnomad4 AMR exome

AF:

0.198

AC:

3212

AN:

16258

Gnomad4 ASJ exome

AF:

0.325

AC:

4155

AN:

12802

Gnomad4 EAS exome

AF:

0.299

AC:

8230

AN:

27554

Gnomad4 SAS exome

AF:

0.273

AC:

10440

AN:

38272

Gnomad4 FIN exome

AF:

0.317

AC:

9735

AN:

30744

Gnomad4 NFE exome

AF:

0.271

AC:

91298

AN:

337344

Gnomad4 Remaining exome

AF:

0.279

AC:

7493

AN:

26810

Heterozygous variant carriers

4857

9714

14572

19429

24286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1590

3180

4770

6360

7950

<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:

0.356

AC:

51733

AN:

145390

Hom.:

9562

Cov.:

AF XY:

0.356

AC XY:

25145

AN XY:

70730

show subpopulations

Gnomad4 AFR

AF:

0.486

AC:

0.485711

AN:

0.485711

Gnomad4 AMR

AF:

0.237

AC:

0.236536

AN:

0.236536

Gnomad4 ASJ

AF:

0.369

AC:

0.369271

AN:

0.369271

Gnomad4 EAS

AF:

0.339

AC:

0.338879

AN:

0.338879

Gnomad4 SAS

AF:

0.280

AC:

0.279725

AN:

0.279725

Gnomad4 FIN

AF:

0.367

AC:

0.366709

AN:

0.366709

Gnomad4 NFE

AF:

0.311

AC:

0.310641

AN:

0.310641

Gnomad4 OTH

AF:

0.323

AC:

0.322645

AN:

0.322645

Heterozygous variant carriers

1454

2908

4362

5816

7270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.108

Hom.:

293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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