rs11045262

Positions:

• chr12-20458824-A-T

Variant summary

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

The NM_000921.5(PDE3A):​c.960+88580A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,006 control chromosomes in the GnomAD database, including 3,144 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 0.20 (3144 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.960+88580A>T		intron_variant		ENST00000359062.4
PDE3A	NM_001378407.1	c.960+88580A>T		intron_variant
PDE3A	NM_001378408.1	c.-68-45822A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.960+88580A>T		intron_variant		1	NM_000921.5	P1
PDE3A	ENST00000542675.1	n.120+88580A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29975 AN: 151886 Hom.: 3134 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.197 AC: 30019 AN: 152006 Hom.: 3144 Cov.: 32 AF XY: 0.197 AC XY: 14643 AN XY: 74328

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.198

Alfa AF: 0.186 Hom.: 338

Bravo AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.65

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: rs11045262; hg19: chr12-20611758;