rs11045392

Variant names:

• chr12-20687905-T-A
• rs11045392
• NM_000921.5:c.*7634T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-20687905-T-A
• chr12-20687905-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000921.5(PDE3A):​c.*7634T>A 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 0.0 (0 hom., cov: 17)
  • Failed GnomAD Quality Control
• 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5	c.*7634T>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000359062.4	NP_000912.3
PDE3A	NM_001378407.1	c.*7634T>A		3_prime_UTR_variant	Exon 14 of 14		NP_001365336.1
PDE3A	NM_001244683.2	c.*7634T>A		3_prime_UTR_variant	Exon 15 of 15		NP_001231612.1
PDE3A	NM_001378408.1	c.*7788T>A		3_prime_UTR_variant	Exon 18 of 18		NP_001365337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062.4	c.*7634T>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_000921.5	ENSP00000351957.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 124092 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 124128 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 58842

African (AFR) AF: 0.00 AC: 0 AN: 29220

American (AMR) AF: 0.00 AC: 0 AN: 11602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3298

East Asian (EAS) AF: 0.00 AC: 0 AN: 4400

South Asian (SAS) AF: 0.00 AC: 0 AN: 3878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62796

Other (OTH) AF: 0.00 AC: 0 AN: 1652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.51
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;