rs10841496

Positions:

• chr12-20368720-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000921.5(PDE3A):​c.-565C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,322 control chromosomes in the GnomAD database, including 15,988 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15988 hom., cov: 29)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.-565C>A		5_prime_UTR_variant	1/16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.-565C>A		5_prime_UTR_variant	1/14		NP_001365336.1
PDE3A	NM_001378408.1	c.-1593C>A		5_prime_UTR_variant	1/18		NP_001365337.1
PDE3A-AS1	NR_186033.1	n.416+1121G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062	c.-565C>A		5_prime_UTR_variant	1/16	1	NM_000921.5	ENSP00000351957.3
PDE3A-AS1	ENST00000535755.1	n.422+1121G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66129 AN: 151204 Hom.: 15982 Cov.: 29

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.437 AC: 66153 AN: 151322 Hom.: 15988 Cov.: 29 AF XY: 0.438 AC XY: 32382 AN XY: 73886

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.454

Alfa AF: 0.505 Hom.: 36170

Bravo AF: 0.437

Asia WGS AF: 0.543 AC: 1885 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10841496; hg19: chr12-20521654;