Genetic Variant PDE3A:c.-83_-74delTGTGTGTGTG (chr12-20369190-CGTGTGTGTGT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000921.5(PDE3A):c.-83_-74delTGTGTGTGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000612 in 653,572 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

PDE3A
NM_000921.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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	Effect	Exon Rank	Protein
PDE3A	NM_000921.5	MANE Select	c.-83_-74delTGTGTGTGTG	5_prime_UTR	Exon 1 of 16	NP_000912.3
PDE3A	NM_001378407.1		c.-83_-74delTGTGTGTGTG	5_prime_UTR	Exon 1 of 14	NP_001365336.1
PDE3A	NM_001378408.1		c.-1111_-1102delTGTGTGTGTG	5_prime_UTR	Exon 1 of 18	NP_001365337.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.-83_-74delTGTGTGTGTG	5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
PDE3A	ENST00000951762.1		c.-83_-74delTGTGTGTGTG	5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+641_422+650delACACACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000394

AC:

AN:

508016

Hom.:

AF XY:

0.00000769

AC XY:

AN XY:

260158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12624

American (AMR)

AF:

0.00

AC:

AN:

16356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12868

East Asian (EAS)

AF:

0.00

AC:

AN:

27648

South Asian (SAS)

AF:

0.00

AC:

AN:

38632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2094

European-Non Finnish (NFE)

AF:

0.00000588

AC:

AN:

339954

Other (OTH)

AF:

0.00

AC:

AN:

26988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145556

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39778

American (AMR)

AF:

0.00

AC:

AN:

14634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4586

South Asian (SAS)

AF:

0.00

AC:

AN:

4528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66050

Other (OTH)

AF:

0.00

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

293

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over