chr12-20369565-A-AGGC
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2
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
NM_000921.5 inframe_insertion
Scores
Not classified
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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: 59AN: 151948Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000844 AC: 13AN: 154006Hom.: 0 AF XY: 0.0000482 AC XY: 4AN XY: 82948
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GnomAD4 exome AF: 0.0000449 AC: 63AN: 1403986Hom.: 1 Cov.: 34 AF XY: 0.0000390 AC XY: 27AN XY: 693068
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at