12-20369190-CGTGTGTGTGTGT-CGTGTGTGTGTGTGT

Variant names:

• chr12-20369190-C-CGT
• rs140759925
• NM_000921.5:c.-75_-74dupTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000921.5(PDE3A):​c.-75_-74dupTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 651,878 control chromosomes in the GnomAD database, including 268 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (180 hom., cov: 0)
  • Exomes 𝑓: 0.044 (88 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-20369190-C-CGT is Benign according to our data. Variant chr12-20369190-C-CGT is described in ClinVar as Benign. ClinVar VariationId is 1269003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	NM_000921.5	MANE Select	c.-75_-74dupTG		5_prime_UTR	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.-75_-74dupTG		5_prime_UTR	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-1103_-1102dupTG		5_prime_UTR	Exon 1 of 18	NP_001365337.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE3A	ENST00000359062.4	TSL:1 MANE Select	c.-75_-74dupTG		5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.-75_-74dupTG		5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+649_422+650dupAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6300 AN: 145488 Hom.: 179 Cov.: 0

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0442 AC: 22393 AN: 506284 Hom.: 88 AF XY: 0.0476 AC XY: 12340 AN XY: 259216

African (AFR) AF: 0.0219 AC: 276 AN: 12614

American (AMR) AF: 0.0372 AC: 606 AN: 16290

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 640 AN: 12850

East Asian (EAS) AF: 0.00185 AC: 51 AN: 27630

South Asian (SAS) AF: 0.122 AC: 4650 AN: 38224

European-Finnish (FIN) AF: 0.0529 AC: 1627 AN: 30776

Middle Eastern (MID) AF: 0.0814 AC: 170 AN: 2088

European-Non Finnish (NFE) AF: 0.0385 AC: 13058 AN: 338896

Other (OTH) AF: 0.0489 AC: 1315 AN: 26916

GnomAD4 genome AF: 0.0433 AC: 6299 AN: 145594 Hom.: 180 Cov.: 0 AF XY: 0.0455 AC XY: 3225 AN XY: 70834

African (AFR) AF: 0.0238 AC: 951 AN: 39880

American (AMR) AF: 0.0427 AC: 626 AN: 14644

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 161 AN: 3406

East Asian (EAS) AF: 0.00219 AC: 10 AN: 4570

South Asian (SAS) AF: 0.153 AC: 693 AN: 4520

European-Finnish (FIN) AF: 0.0632 AC: 595 AN: 9416

Middle Eastern (MID) AF: 0.107 AC: 30 AN: 280

European-Non Finnish (NFE) AF: 0.0470 AC: 3106 AN: 66016

Other (OTH) AF: 0.0550 AC: 110 AN: 2000

Alfa AF: 0.00935 Hom.: 293

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs140759925; hg19: chr12-20522124;