chr12-20369553-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000921.5(PDE3A):c.269A>G(p.Glu90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,558,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000921.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE3A | NM_000921.5 | c.269A>G | p.Glu90Gly | missense_variant | 1/16 | ENST00000359062.4 | |
PDE3A | NM_001378407.1 | c.269A>G | p.Glu90Gly | missense_variant | 1/14 | ||
PDE3A | NM_001378408.1 | c.-760A>G | 5_prime_UTR_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE3A | ENST00000359062.4 | c.269A>G | p.Glu90Gly | missense_variant | 1/16 | 1 | NM_000921.5 | P1 | |
PDE3A-AS1 | ENST00000535755.1 | n.422+288T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000770 AC: 117AN: 151912Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000125 AC: 20AN: 159418Hom.: 0 AF XY: 0.000105 AC XY: 9AN XY: 85690
GnomAD4 exome AF: 0.0000754 AC: 106AN: 1406552Hom.: 0 Cov.: 34 AF XY: 0.0000691 AC XY: 48AN XY: 694366
GnomAD4 genome ? AF: 0.000770 AC: 117AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.000780 AC XY: 58AN XY: 74316
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.269A>G (p.E90G) alteration is located in exon 1 (coding exon 1) of the PDE3A gene. This alteration results from a A to G substitution at nucleotide position 269, causing the glutamic acid (E) at amino acid position 90 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
PDE3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 11, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at