12-20678843-T-C

Position:

• chr12-20678843-T-C

Variant summary

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

The NM_000921.5(PDE3A):​c.3185-1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,136 control chromosomes in the GnomAD database, including 37,589 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 0.70 (37589 hom., cov: 33)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.3185-1187T>C		intron_variant		ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.2879-1187T>C		intron_variant			NP_001365336.1
PDE3A	NM_001244683.2	c.2219-1187T>C		intron_variant			NP_001231612.1
PDE3A	NM_001378408.1	c.2297+371T>C		intron_variant			NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.3185-1187T>C		intron_variant		1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000544307.1	n.2482-1187T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106548 AN: 152018 Hom.: 37546 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.701 AC: 106654 AN: 152136 Hom.: 37589 Cov.: 33 AF XY: 0.701 AC XY: 52173 AN XY: 74374

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.703

Alfa AF: 0.684 Hom.: 47050

Bravo AF: 0.698

Asia WGS AF: 0.754 AC: 2624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7137534; hg19: chr12-20831777;