12-20409973-A-G

Variant names:

• chr12-20409973-A-G
• rs1444629
• NM_000921.5:c.960+39729A>G

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+39729A>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 152,046 control chromosomes in the GnomAD database, including 31,824 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 (31824 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 7 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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+39729A>G		intron_variant	Intron 1 of 15	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.960+39729A>G		intron_variant	Intron 1 of 13		NP_001365336.1
PDE3A	NM_001378408.1	c.-69+39729A>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+39729A>G		intron_variant	Intron 1 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000542675.1	n.120+39729A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96219 AN: 151928 Hom.: 31807 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.633 AC: 96281 AN: 152046 Hom.: 31824 Cov.: 32 AF XY: 0.641 AC XY: 47651 AN XY: 74320

African (AFR) AF: 0.430 AC: 17823 AN: 41442

American (AMR) AF: 0.690 AC: 10543 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2108 AN: 3468

East Asian (EAS) AF: 0.885 AC: 4575 AN: 5170

South Asian (SAS) AF: 0.709 AC: 3418 AN: 4822

European-Finnish (FIN) AF: 0.805 AC: 8506 AN: 10568

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

European-Non Finnish (NFE) AF: 0.693 AC: 47094 AN: 67978

Other (OTH) AF: 0.613 AC: 1295 AN: 2114

Alfa AF: 0.669 Hom.: 56730

Bravo AF: 0.616

Asia WGS AF: 0.774 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.60
PhyloP100		0.094
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: rs1444629; hg19: chr12-20562907;