12-20369180-A-AGCGT

Variant summary

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

The NM_000921.5(PDE3A):c.-95_-92dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 619,776 control chromosomes in the GnomAD database, including 7,682 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (4443 hom., cov: 22)
  • Exomes 𝑓: 0.20 (3239 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.184

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 12-20369180-A-AGCGT is Benign according to our data. Variant chr12-20369180-A-AGCGT is described in ClinVar as [Benign]. Clinvar id is 1234823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.-95_-92dup		5_prime_UTR_variant	1/16	ENST00000359062.4
PDE3A	NM_001378407.1	c.-95_-92dup		5_prime_UTR_variant	1/14
PDE3A	NM_001378408.1	c.-1123_-1120dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.-95_-92dup		5_prime_UTR_variant	1/16	1	NM_000921.5	P1
PDE3A-AS1	ENST00000535755.1	n.422+660_422+661insACGC		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 32398 AN: 125132 Hom.: 4446 Cov.: 22

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.200 AC: 98796 AN: 494544 Hom.: 3239 AF XY: 0.201 AC XY: 51077 AN XY: 254108

Gnomad4 AFR exome AF: 0.0489

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.0341

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.259 AC: 32388 AN: 125232 Hom.: 4443 Cov.: 22 AF XY: 0.251 AC XY: 15240 AN XY: 60624

Gnomad4 AFR AF: 0.0961

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.268

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: rs71039938; hg19: chr12-20522114;