dbSNP rs71039938: PDE3A:c.-95_-92delCGTG (chr12-20369180-AGCGT-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000921.5(PDE3A):c.-95_-92delCGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 626,952 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 0.00012 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

PDE3A
NM_000921.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.668

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene.

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.-95_-92delCGTG	5_prime_UTR	Exon 1 of 16	NP_000912.3
PDE3A	NM_001378407.1		c.-95_-92delCGTG	5_prime_UTR	Exon 1 of 14	NP_001365336.1
PDE3A	NM_001378408.1		c.-1123_-1120delCGTG	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.-95_-92delCGTG	5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
PDE3A	ENST00000951762.1		c.-95_-92delCGTG	5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+657_422+660delACGC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000120

AC:

AN:

125440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000240

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000652

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

501410

Hom.:

AF XY:

0.0000582

AC XY:

AN XY:

257628

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

14016

American (AMR)

AF:

0.000116

AC:

AN:

17258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13286

East Asian (EAS)

AF:

0.0000660

AC:

AN:

30292

South Asian (SAS)

AF:

0.000104

AC:

AN:

38582

European-Finnish (FIN)

AF:

0.0000320

AC:

AN:

31262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2038

European-Non Finnish (NFE)

AF:

0.0000397

AC:

AN:

327384

Other (OTH)

AF:

0.00

AC:

AN:

27292

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000367034), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.368

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000119

AC:

AN:

125542

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

60776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28168

American (AMR)

AF:

0.000720

AC:

AN:

13896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3088

East Asian (EAS)

AF:

0.000240

AC:

AN:

4158

South Asian (SAS)

AF:

0.00

AC:

AN:

3930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000652

AC:

AN:

61338

Other (OTH)

AF:

0.00

AC:

AN:

1776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.67

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over