12-20409660-A-G

Variant names:

• chr12-20409660-A-G
• rs10505865
• NM_000921.5:c.960+39416A>G

Variant summary

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

The NM_000921.5(PDE3A):​c.960+39416A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,962 control chromosomes in the GnomAD database, including 31,806 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 0.63 (31806 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.960+39416A>G		intron_variant	Intron 1 of 15	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.960+39416A>G		intron_variant	Intron 1 of 13		NP_001365336.1
PDE3A	NM_001378408.1	c.-69+39416A>G		intron_variant	Intron 1 of 17		NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.960+39416A>G		intron_variant	Intron 1 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000542675.1	n.120+39416A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96170 AN: 151844 Hom.: 31789 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.633 AC: 96232 AN: 151962 Hom.: 31806 Cov.: 32 AF XY: 0.641 AC XY: 47629 AN XY: 74292

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.612

Alfa AF: 0.656 Hom.: 4172

Bravo AF: 0.616

Asia WGS AF: 0.775 AC: 2694 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.37

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: rs10505865; hg19: chr12-20562594;