rs10841530

Variant names:

• chr12-20446178-A-G
• rs10841530
• NM_000921.5:c.960+75934A>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+75934A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,102 control chromosomes in the GnomAD database, including 9,022 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 0.31 (9022 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.960+75934A>G		intron_variant	Intron 1 of 15	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.960+75934A>G		intron_variant	Intron 1 of 13		NP_001365336.1
PDE3A	NM_001378408.1	c.-68-58468A>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+75934A>G		intron_variant	Intron 1 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000542675.1	n.120+75934A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46701 AN: 151984 Hom.: 9025 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.307 AC: 46694 AN: 152102 Hom.: 9022 Cov.: 32 AF XY: 0.314 AC XY: 23309 AN XY: 74340

African (AFR) AF: 0.0828 AC: 3439 AN: 41550

American (AMR) AF: 0.312 AC: 4766 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3239 AN: 5158

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4022 AN: 10554

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.387 AC: 26299 AN: 67974

Other (OTH) AF: 0.329 AC: 693 AN: 2108

Alfa AF: 0.356 Hom.: 29819

Bravo AF: 0.289

Asia WGS AF: 0.548 AC: 1902 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.91
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: rs10841530; hg19: chr12-20599112;