12-20369190-CGTGTGTGTGTGT-CGTGTGTGTGT

Variant names:

• chr12-20369190-CGT-C
• rs140759925
• NM_000921.5:c.-75_-74delTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000921.5(PDE3A):​c.-75_-74delTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 633,702 control chromosomes in the GnomAD database, including 305 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (282 hom., cov: 0)
  • Exomes 𝑓: 0.0098 (23 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.-75_-74delTG		5_prime_UTR_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.-75_-74delTG		5_prime_UTR_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1	c.-1103_-1102delTG		5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1	n.416+649_416+650delAC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062	c.-75_-74delTG		5_prime_UTR_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3
PDE3A-AS1	ENST00000535755.1	n.422+649_422+650delAC		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 4903 AN: 145484 Hom.: 281 Cov.: 0

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.00133

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000742

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.00984 AC: 4801 AN: 488112 Hom.: 23 AF XY: 0.00953 AC XY: 2384 AN XY: 250086

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.00385

Gnomad4 EAS exome AF: 0.0124

Gnomad4 SAS exome AF: 0.0100

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.00538

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0337 AC: 4912 AN: 145590 Hom.: 282 Cov.: 0 AF XY: 0.0337 AC XY: 2390 AN XY: 70838

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.00263

Gnomad4 SAS AF: 0.00133

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.000742

Gnomad4 OTH AF: 0.0260

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;