12-20369515-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000921.5(PDE3A):c.231G>A(p.Leu77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,560,594 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0087 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 23 hom. )
Consequence
PDE3A
NM_000921.5 synonymous
NM_000921.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.26
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 12-20369515-G-A is Benign according to our data. Variant chr12-20369515-G-A is described in ClinVar as [Benign]. Clinvar id is 717258.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=3.26 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00872 (1328/152332) while in subpopulation AFR AF= 0.0304 (1263/41584). AF 95% confidence interval is 0.029. There are 21 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1327 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE3A | NM_000921.5 | c.231G>A | p.Leu77= | synonymous_variant | 1/16 | ENST00000359062.4 | |
PDE3A | NM_001378407.1 | c.231G>A | p.Leu77= | synonymous_variant | 1/14 | ||
PDE3A | NM_001378408.1 | c.-798G>A | 5_prime_UTR_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE3A | ENST00000359062.4 | c.231G>A | p.Leu77= | synonymous_variant | 1/16 | 1 | NM_000921.5 | P1 | |
PDE3A-AS1 | ENST00000535755.1 | n.422+326C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00872 AC: 1327AN: 152214Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00199 AC: 326AN: 164168Hom.: 5 AF XY: 0.00151 AC XY: 133AN XY: 87844
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GnomAD4 exome AF: 0.000842 AC: 1186AN: 1408262Hom.: 23 Cov.: 34 AF XY: 0.000721 AC XY: 501AN XY: 695314
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at