NM_000921.5:c.-77_-74delTGTG

Variant names:

• chr12-20369190-CGTGT-C
• rs140759925
• NM_000921.5:c.-77_-74delTGTG

Variant summary

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

The NM_000921.5(PDE3A):​c.-77_-74delTGTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 649,772 control chromosomes in the GnomAD database, including 19,981 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (9562 hom., cov: 0)
  • Exomes 𝑓: 0.28 (10419 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.962
• 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-CGTGT-C is Benign according to our data. Variant chr12-20369190-CGTGT-C is described in ClinVar as Benign. ClinVar VariationId is 1241874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 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.-77_-74delTGTG		5_prime_UTR	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.-77_-74delTGTG		5_prime_UTR	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-1105_-1102delTGTG		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.-77_-74delTGTG		5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.-77_-74delTGTG		5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+647_422+650delACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.356 AC: 51693 AN: 145282 Hom.: 9551 Cov.: 0

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.278 AC: 140326 AN: 504382 Hom.: 10419 AF XY: 0.277 AC XY: 71575 AN XY: 258254

African (AFR) AF: 0.422 AC: 5274 AN: 12512

American (AMR) AF: 0.198 AC: 3212 AN: 16258

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 4155 AN: 12802

East Asian (EAS) AF: 0.299 AC: 8230 AN: 27554

South Asian (SAS) AF: 0.273 AC: 10440 AN: 38272

European-Finnish (FIN) AF: 0.317 AC: 9735 AN: 30744

Middle Eastern (MID) AF: 0.234 AC: 489 AN: 2086

European-Non Finnish (NFE) AF: 0.271 AC: 91298 AN: 337344

Other (OTH) AF: 0.279 AC: 7493 AN: 26810

GnomAD4 genome AF: 0.356 AC: 51733 AN: 145390 Hom.: 9562 Cov.: 0 AF XY: 0.356 AC XY: 25145 AN XY: 70730

African (AFR) AF: 0.486 AC: 19341 AN: 39820

American (AMR) AF: 0.237 AC: 3461 AN: 14632

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1257 AN: 3404

East Asian (EAS) AF: 0.339 AC: 1548 AN: 4568

South Asian (SAS) AF: 0.280 AC: 1261 AN: 4508

European-Finnish (FIN) AF: 0.367 AC: 3450 AN: 9408

Middle Eastern (MID) AF: 0.211 AC: 59 AN: 280

European-Non Finnish (NFE) AF: 0.311 AC: 20475 AN: 65912

Other (OTH) AF: 0.323 AC: 644 AN: 1996

Alfa AF: 0.108 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		0.96

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;