Genetic Variant NM_000921.5:c.77G>A (chr12-20369361-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000921.5(PDE3A):c.77G>A(p.Gly26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PDE3A
NM_000921.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Publications

0 publications found

Variant links:

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 links:

PDE3A-AS1 (HGNC:40436): (PDE3A antisense RNA 1)

PDE3A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073337644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDE3A	NM_000921.5	MANE Select	c.77G>A	p.Gly26Asp	missense	Exon 1 of 16	NP_000912.3
PDE3A	NM_001378407.1		c.77G>A	p.Gly26Asp	missense	Exon 1 of 14	NP_001365336.1
PDE3A	NM_001378408.1		c.-952G>A		5_prime_UTR	Exon 1 of 18	NP_001365337.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.77G>A	p.Gly26Asp	missense	Exon 1 of 16	ENSP00000351957.3	Q14432
PDE3A	ENST00000951762.1		c.77G>A	p.Gly26Asp	missense	Exon 1 of 15	ENSP00000621821.1
PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+480C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396696

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31564

American (AMR)

AF:

0.00

AC:

AN:

35748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25134

East Asian (EAS)

AF:

0.00

AC:

AN:

35742

South Asian (SAS)

AF:

0.00

AC:

AN:

79134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5240

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078744

Other (OTH)

AF:

0.00

AC:

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.38

M_CAP

Benign

0.065

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PhyloP100

1.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.99

REVEL

Benign

0.10

Sift

Uncertain

0.0090

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.10

MutPred

0.078

Gain of solvent accessibility (P = 0.0638)

MVP

0.28

MPC

1.1

ClinPred

0.12

GERP RS

0.59

Varity_R

0.12

gMVP

0.27

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over