12-20687905-T-C

Position:

• chr12-20687905-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.*7634T>C		3_prime_UTR_variant	16/16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001244683.2	c.*7634T>C		3_prime_UTR_variant	15/15		NP_001231612.1
PDE3A	NM_001378407.1	c.*7634T>C		3_prime_UTR_variant	14/14		NP_001365336.1
PDE3A	NM_001378408.1	c.*7788T>C		3_prime_UTR_variant	18/18		NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.*7634T>C		3_prime_UTR_variant	16/16	1	NM_000921.5	ENSP00000351957	P1

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

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.598

Alfa AF: 0.611 Hom.: 57465

Asia WGS AF: 0.660 AC: 2272 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045392; hg19: chr12-20840839;