12-20687905-T-C

Variant names:

• chr12-20687905-T-C
• rs11045392
• NM_000921.5:c.*7634T>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.*7634T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.60 (21223 hom., cov: 17)
• Consequence: PDE3A NM_000921.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	NM_000921.5	MANE Select	c.*7634T>C		3_prime_UTR	Exon 16 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.*7634T>C		3_prime_UTR	Exon 14 of 14	NP_001365336.1
	PDE3A	NM_001244683.2		c.*7634T>C		3_prime_UTR	Exon 15 of 15	NP_001231612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.*7634T>C		3_prime_UTR	Exon 16 of 16	ENSP00000351957.3	Q14432

Frequencies

GnomAD3 genomes AF: 0.598 AC: 73849 AN: 123514 Hom.: 21223 Cov.: 17

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.598 AC: 73853 AN: 123550 Hom.: 21223 Cov.: 17 AF XY: 0.600 AC XY: 35151 AN XY: 58564

African (AFR) AF: 0.502 AC: 14598 AN: 29070

American (AMR) AF: 0.506 AC: 5840 AN: 11538

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2444 AN: 3296

East Asian (EAS) AF: 0.761 AC: 3339 AN: 4388

South Asian (SAS) AF: 0.723 AC: 2786 AN: 3854

European-Finnish (FIN) AF: 0.636 AC: 3895 AN: 6124

Middle Eastern (MID) AF: 0.652 AC: 159 AN: 244

European-Non Finnish (NFE) AF: 0.627 AC: 39226 AN: 62528

Other (OTH) AF: 0.598 AC: 983 AN: 1644

Alfa AF: 0.599 Hom.: 87607

Asia WGS AF: 0.660 AC: 2272 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.53
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11045392; hg19: chr12-20840839;