12-20369190-CGTGTGTGTGTGT-CGTGTGTGTGTGTGTGT

Variant names:

• chr12-20369190-C-CGTGT
• rs140759925
• NM_000921.5:c.-77_-74dupTGTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000921.5(PDE3A):​c.-77_-74dupTGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 653,624 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 0.00024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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-AS1 (HGNC:40436): (PDE3A antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000240 AC: 35 AN: 145556 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000273

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000218

Gnomad SAS AF: 0.000221

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000288

Gnomad OTH AF: 0.000505

GnomAD4 exome AF: 0.000272 AC: 138 AN: 507960 Hom.: 0 AF XY: 0.000327 AC XY: 85 AN XY: 260132

Gnomad4 AFR exome AF: 0.000317

Gnomad4 AMR exome AF: 0.000183

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.0000362

Gnomad4 SAS exome AF: 0.000570

Gnomad4 FIN exome AF: 0.000259

Gnomad4 NFE exome AF: 0.000259

Gnomad4 OTH exome AF: 0.000296

GnomAD4 genome AF: 0.000240 AC: 35 AN: 145664 Hom.: 0 Cov.: 0 AF XY: 0.000155 AC XY: 11 AN XY: 70874

Gnomad4 AFR AF: 0.000226

Gnomad4 AMR AF: 0.000273

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000219

Gnomad4 SAS AF: 0.000221

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000288

Gnomad4 OTH AF: 0.000500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140759925; hg19: chr12-20522124;