Genetic Variant PDE3A:c.-99_-92dupCGTGCGTG (chr12-20369180-A-AGCGTGCGT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000921.5(PDE3A):c.-99_-92dupCGTGCGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 626,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PDE3A
NM_000921.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

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 0 ACMG points.

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.-99_-92dupCGTGCGTG	5_prime_UTR	Exon 1 of 16	NP_000912.3
PDE3A	NM_001378407.1		c.-99_-92dupCGTGCGTG	5_prime_UTR	Exon 1 of 14	NP_001365336.1
PDE3A	NM_001378408.1		c.-1127_-1120dupCGTGCGTG	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.-99_-92dupCGTGCGTG	5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
PDE3A	ENST00000951762.1		c.-99_-92dupCGTGCGTG	5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+653_422+660dupACGCACGC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000159

AC:

AN:

125442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000144

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000997

AC:

AN:

501418

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

257632

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:

14018

American (AMR)

AF:

0.00

AC:

AN:

17258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13286

East Asian (EAS)

AF:

0.00

AC:

AN:

30294

South Asian (SAS)

AF:

0.0000259

AC:

AN:

38582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31262

Middle Eastern (MID)

AF:

0.000491

AC:

AN:

2038

European-Non Finnish (NFE)

AF:

0.00000916

AC:

AN:

327388

Other (OTH)

AF:

0.00

AC:

AN:

27292

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00384931), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.0000159

AC:

AN:

125442

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

60688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28084

American (AMR)

AF:

0.000144

AC:

AN:

13876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3088

East Asian (EAS)

AF:

0.00

AC:

AN:

4166

South Asian (SAS)

AF:

0.00

AC:

AN:

3924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61340

Other (OTH)

AF:

0.00

AC:

AN:

1758

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

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

0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-20369180-AGCGT-AGCGTGCGTGCGT

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