12-20369565-A-AGGC

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_000921.5(PDE3A):c.293_295dup(p.Ala98dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000784 in 1,555,934 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (1 hom.)
• Consequence: PDE3A NM_000921.5 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28

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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000921.5
• BP6: Variant 12-20369565-A-AGGC is Benign according to our data. Variant chr12-20369565-A-AGGC is described in ClinVar as [Likely_benign]. Clinvar id is 2769316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE3A	NM_000921.5	c.293_295dup	p.Ala98dup	inframe_insertion	1/16	ENST00000359062.4
PDE3A	NM_001378407.1	c.293_295dup	p.Ala98dup	inframe_insertion	1/14
PDE3A	NM_001378408.1	c.-736_-734dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE3A	ENST00000359062.4	c.293_295dup	p.Ala98dup	inframe_insertion	1/16	1	NM_000921.5	P1
PDE3A-AS1	ENST00000535755.1	n.422+275_422+276insGCC		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 151948 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD3 exomes AF: 0.0000844 AC: 13 AN: 154006 Hom.: 0 AF XY: 0.0000482 AC XY: 4 AN XY: 82948

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.0000400

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000901

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.0000449 AC: 63 AN: 1403986 Hom.: 1 Cov.: 34 AF XY: 0.0000390 AC XY: 27 AN XY: 693068

Gnomad4 AFR exome AF: 0.000998

Gnomad4 AMR exome AF: 0.0000274

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000113

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000138

Gnomad4 OTH exome AF: 0.000103

GnomAD4 genome AF: 0.000388 AC: 59 AN: 151948 Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26 AN XY: 74216

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 20, 2023

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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: rs760131099; hg19: chr12-20522499;