rs11614805

Variant names:

• chr12-20592602-C-T
• rs11614805
• NM_000921.5:c.1012-20841C>T

Variant summary

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

The NM_000921.5(PDE3A):​c.1012-20841C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,090 control chromosomes in the GnomAD database, including 1,167 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 0.097 (1167 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.1012-20841C>T		intron_variant	Intron 2 of 15	ENST00000359062.4	NP_000912.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.1012-20841C>T		intron_variant	Intron 2 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000544307.1	n.308+20431C>T		intron_variant	Intron 1 of 14	1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14667 AN: 151972 Hom.: 1161 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0584

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0787

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

GnomAD4 genome AF: 0.0967 AC: 14703 AN: 152090 Hom.: 1167 Cov.: 32 AF XY: 0.0928 AC XY: 6896 AN XY: 74328

African (AFR) AF: 0.221 AC: 9151 AN: 41458

American (AMR) AF: 0.0592 AC: 905 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3466

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5176

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4820

European-Finnish (FIN) AF: 0.0395 AC: 418 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3568 AN: 68000

Other (OTH) AF: 0.0779 AC: 164 AN: 2106

Alfa AF: 0.0587 Hom.: 352

Bravo AF: 0.103

Asia WGS AF: 0.0480 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.54
PhyloP100		-1.7
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: rs11614805; hg19: chr12-20745536;