12-20678843-T-C

Variant names:

• chr12-20678843-T-C
• rs7137534
• NM_000921.5:c.3185-1187T>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.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
• Publications: 6 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=-0.92).
• 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 rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.3185-1187T>C		intron_variant	Intron 15 of 15	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.2879-1187T>C		intron_variant	Intron 13 of 13		NP_001365336.1
PDE3A	NM_001244683.2	c.2219-1187T>C		intron_variant	Intron 14 of 14		NP_001231612.1
PDE3A	NM_001378408.1	c.2297+371T>C		intron_variant	Intron 17 of 17		NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.3185-1187T>C		intron_variant	Intron 15 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000544307.1	n.2482-1187T>C		intron_variant	Intron 14 of 14	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

African (AFR) AF: 0.743 AC: 30839 AN: 41486

American (AMR) AF: 0.628 AC: 9604 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3468

East Asian (EAS) AF: 0.840 AC: 4341 AN: 5166

South Asian (SAS) AF: 0.730 AC: 3519 AN: 4822

European-Finnish (FIN) AF: 0.691 AC: 7315 AN: 10584

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45832 AN: 68008

Other (OTH) AF: 0.703 AC: 1481 AN: 2106

Alfa AF: 0.684 Hom.: 59433

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
PhyloP100		-1.4
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: rs7137534; hg19: chr12-20831777;