12-20369190-CGTGTGTGTGTGT-CGTGTGTGTGTGTGTGTGT

Variant names:

• chr12-20369190-C-CGTGTGT
• rs140759925
• NM_000921.5:c.-79_-74dupTGTGTG

Variant summary

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

The NM_000921.5(PDE3A):​c.-79_-74dupTGTGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 653,678 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (1 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 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.-79_-74dupTGTGTG		5_prime_UTR_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.-79_-74dupTGTGTG		5_prime_UTR_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1	c.-1107_-1102dupTGTGTG		5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1	n.416+645_416+650dupACACAC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062	c.-79_-74dupTGTGTG		5_prime_UTR_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3
PDE3A-AS1	ENST00000535755.1	n.422+645_422+650dupACACAC		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 26 AN: 145556 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00392

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000454

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000246 AC: 125 AN: 508014 Hom.: 1 AF XY: 0.000242 AC XY: 63 AN XY: 260154

Gnomad4 AFR exome AF: 0.0000792

Gnomad4 AMR exome AF: 0.000183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00300

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000765

Gnomad4 OTH exome AF: 0.000148

GnomAD4 genome AF: 0.000178 AC: 26 AN: 145664 Hom.: 0 Cov.: 0 AF XY: 0.000254 AC XY: 18 AN XY: 70874

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00416

Gnomad4 SAS AF: 0.000884

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000454

Gnomad4 OTH AF: 0.00

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;