12-20369190-CGTGT-C

Variant summary

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

The NM_000921.5(PDE3A):c.-77_-74del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 649,772 control chromosomes in the GnomAD database, including 19,981 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (9562 hom., cov: 0)
  • Exomes 𝑓: 0.28 (10419 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.962

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-CGTGT-C is Benign according to our data. Variant chr12-20369190-CGTGT-C is described in ClinVar as [Benign]. Clinvar id is 1241874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.-77_-74del		5_prime_UTR_variant	1/16	ENST00000359062.4
PDE3A	NM_001378407.1	c.-77_-74del		5_prime_UTR_variant	1/14
PDE3A	NM_001378408.1	c.-1105_-1102del		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.-77_-74del		5_prime_UTR_variant	1/16	1	NM_000921.5	P1
PDE3A-AS1	ENST00000535755.1	n.422+647_422+650del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 51693 AN: 145282 Hom.: 9551 Cov.: 0

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.278 AC: 140326 AN: 504382 Hom.: 10419 AF XY: 0.277 AC XY: 71575 AN XY: 258254

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.356 AC: 51733 AN: 145390 Hom.: 9562 Cov.: 0 AF XY: 0.356 AC XY: 25145 AN XY: 70730

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.323

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 19, 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;