12-20413063-T-C

Variant names:

• chr12-20413063-T-C
• rs1444645
• NM_000921.5:c.960+42819T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000921.5(PDE3A):​c.960+42819T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,092 control chromosomes in the GnomAD database, including 30,803 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 0.62 (30803 hom., cov: 33)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 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 Gene-Disease associations (from GenCC):

• brachydactyly-arterial hypertension syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	NM_000921.5	MANE Select	c.960+42819T>C		intron	N/A	NP_000912.3
	PDE3A	NM_001378407.1		c.960+42819T>C		intron	N/A	NP_001365336.1
	PDE3A	NM_001378408.1		c.-69+42819T>C		intron	N/A	NP_001365337.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.960+42819T>C		intron	N/A	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.960+42819T>C		intron	N/A	ENSP00000621821.1
	PDE3A	ENST00000542675.1	TSL:3	n.120+42819T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93908 AN: 151974 Hom.: 30791 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.618 AC: 93957 AN: 152092 Hom.: 30803 Cov.: 33 AF XY: 0.627 AC XY: 46577 AN XY: 74344

African (AFR) AF: 0.382 AC: 15824 AN: 41460

American (AMR) AF: 0.687 AC: 10497 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3466

East Asian (EAS) AF: 0.884 AC: 4583 AN: 5182

South Asian (SAS) AF: 0.709 AC: 3419 AN: 4822

European-Finnish (FIN) AF: 0.804 AC: 8507 AN: 10576

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46840 AN: 67998

Other (OTH) AF: 0.599 AC: 1266 AN: 2112

Alfa AF: 0.636 Hom.: 4146

Bravo AF: 0.599

Asia WGS AF: 0.769 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.51
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1444645; hg19: chr12-20565997;