rs1348582

Variant names:

• chr12-20378822-T-C
• rs1348582
• NM_000921.5:c.960+8578T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-20378822-T-C
• chr12-20378822-T-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+8578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,566 control chromosomes in the GnomAD database, including 5,549 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 0.25 (5549 hom., cov: 32)
• Consequence: PDE3A NM_000921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 16 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.960+8578T>C		intron_variant	Intron 1 of 15	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.960+8578T>C		intron_variant	Intron 1 of 13		NP_001365336.1
PDE3A	NM_001378408.1	c.-69+8578T>C		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+8578T>C		intron_variant	Intron 1 of 15	1	NM_000921.5	ENSP00000351957.3
PDE3A	ENST00000542675.1	n.120+8578T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37677 AN: 151448 Hom.: 5533 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.249 AC: 37721 AN: 151566 Hom.: 5549 Cov.: 32 AF XY: 0.251 AC XY: 18571 AN XY: 74094

African (AFR) AF: 0.384 AC: 15875 AN: 41364

American (AMR) AF: 0.317 AC: 4822 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3456

East Asian (EAS) AF: 0.374 AC: 1924 AN: 5140

South Asian (SAS) AF: 0.179 AC: 865 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1943 AN: 10578

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10981 AN: 67714

Other (OTH) AF: 0.244 AC: 513 AN: 2100

Alfa AF: 0.194 Hom.: 9585

Bravo AF: 0.269

Asia WGS AF: 0.294 AC: 1023 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.98
DANN	Benign	0.69
PhyloP100		-0.34
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: rs1348582; hg19: chr12-20531756;