12-20369190-C-CGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000921.5(PDE3A):c.-75_-74dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 651,878 control chromosomes in the GnomAD database, including 268 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (180 hom., cov: 0)
  • Exomes 𝑓: 0.044 (88 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115

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-AS1 (HGNC:40436): (PDE3A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-20369190-C-CGT is Benign according to our data. Variant chr12-20369190-C-CGT is described in ClinVar as [Benign]. Clinvar id is 1269003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.-75_-74dup		5_prime_UTR_variant	1/16	ENST00000359062.4
PDE3A	NM_001378407.1	c.-75_-74dup		5_prime_UTR_variant	1/14
PDE3A	NM_001378408.1	c.-1103_-1102dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.-75_-74dup		5_prime_UTR_variant	1/16	1	NM_000921.5	P1
PDE3A-AS1	ENST00000535755.1	n.422+650_422+651insAC		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6300 AN: 145488 Hom.: 179 Cov.: 0

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0442 AC: 22393 AN: 506284 Hom.: 88 AF XY: 0.0476 AC XY: 12340 AN XY: 259216

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.0372

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.00185

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.0529

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.0489

GnomAD4 genome AF: 0.0433 AC: 6299 AN: 145594 Hom.: 180 Cov.: 0 AF XY: 0.0455 AC XY: 3225 AN XY: 70834

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.00219

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0632

Gnomad4 NFE AF: 0.0470

Gnomad4 OTH AF: 0.0550

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140759925; hg19: chr12-20522124;