chr12-20368720-C-A

Variant names:

• chr12-20368720-C-A
• rs10841496
• NM_000921.5:c.-565C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.-565C>A		5_prime_UTR_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.-565C>A		5_prime_UTR_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1	c.-1593C>A		5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1	n.416+1121G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.-565C>A		5_prime_UTR_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3
PDE3A-AS1	ENST00000535755.1	n.422+1121G>T		intron_variant	Intron 1 of 1	4
PDE3A-AS1	ENST00000745828.1	n.114+1282G>T		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.223 AC: 9229 AN: 41308

American (AMR) AF: 0.581 AC: 8858 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2781 AN: 5006

South Asian (SAS) AF: 0.525 AC: 2513 AN: 4790

European-Finnish (FIN) AF: 0.472 AC: 4934 AN: 10452

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34592 AN: 67754

Other (OTH) AF: 0.454 AC: 954 AN: 2102

Alfa AF: 0.492 Hom.: 80392

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
PhyloP100		-0.33
PromoterAI		-0.028	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10841496; hg19: chr12-20521654;