Genetic Variant NM_000921.5:c.-95_-92dupCGTG (chr12-20369180-A-AGCGT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000921.5(PDE3A):c.-95_-92dupCGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 619,776 control chromosomes in the GnomAD database, including 7,682 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 4443 hom., cov: 22)

Exomes 𝑓: 0.20 ( 3239 hom. )

Consequence

PDE3A
NM_000921.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.184

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-20369180-A-AGCGT is Benign according to our data. Variant chr12-20369180-A-AGCGT is described in ClinVar as [Benign]. Clinvar id is 1234823.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDE3A	NM_000921.5 link	c.-95_-92dupCGTG	5_prime_UTR_variant	Exon 1 of 16	ENST00000359062.4	NP_000912.3	Q14432
PDE3A	NM_001378407.1 link	c.-95_-92dupCGTG	5_prime_UTR_variant	Exon 1 of 14		NP_001365336.1
PDE3A	NM_001378408.1 link	c.-1123_-1120dupCGTG	5_prime_UTR_variant	Exon 1 of 18		NP_001365337.1
PDE3A-AS1	NR_186033.1 link	n.416+657_416+660dupACGC	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE3A	ENST00000359062 link	c.-95_-92dupCGTG		5_prime_UTR_variant	Exon 1 of 16	1	NM_000921.5	ENSP00000351957.3		Q14432
PDE3A-AS1	ENST00000535755.1 link	n.422+657_422+660dupACGC		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

32398

AN:

125132

Hom.:

4446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0964

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.0644

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.368

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.200

AC:

98796

AN:

494544

Hom.:

3239

AF XY:

0.201

AC XY:

51077

AN XY:

254108

show subpopulations

Gnomad4 AFR exome

AF:

0.0489

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.0341

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.259

AC:

32388

AN:

125232

Hom.:

4443

Cov.:

AF XY:

0.251

AC XY:

15240

AN XY:

60624

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.0643

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.268

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over