NM_000921.5:c.-75_-74delTG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000921.5(PDE3A):​c.-75_-74delTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 633,702 control chromosomes in the GnomAD database, including 305 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (282 hom., cov: 0)
  • Exomes 𝑓: 0.0098 (23 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 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_-74delTG		5_prime_UTR	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.-75_-74delTG		5_prime_UTR	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-1103_-1102delTG		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_-74delTG		5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.-75_-74delTG		5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+649_422+650delAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 4903 AN: 145484 Hom.: 281 Cov.: 0

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.00133

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000742

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.00984 AC: 4801 AN: 488112 Hom.: 23 AF XY: 0.00953 AC XY: 2384 AN XY: 250086

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.114 AC: 1409 AN: 12354

American (AMR) AF: 0.0259 AC: 384 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.00385 AC: 48 AN: 12464

East Asian (EAS) AF: 0.0124 AC: 292 AN: 23610

South Asian (SAS) AF: 0.0100 AC: 376 AN: 37532

European-Finnish (FIN) AF: 0.00489 AC: 144 AN: 29474

Middle Eastern (MID) AF: 0.00836 AC: 17 AN: 2034

European-Non Finnish (NFE) AF: 0.00538 AC: 1775 AN: 329964

Other (OTH) AF: 0.0138 AC: 356 AN: 25842

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0337 AC: 4912 AN: 145590 Hom.: 282 Cov.: 0 AF XY: 0.0337 AC XY: 2390 AN XY: 70838

African (AFR) AF: 0.115 AC: 4597 AN: 39858

American (AMR) AF: 0.0132 AC: 193 AN: 14650

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3406

East Asian (EAS) AF: 0.00263 AC: 12 AN: 4568

South Asian (SAS) AF: 0.00133 AC: 6 AN: 4524

European-Finnish (FIN) AF: 0.000106 AC: 1 AN: 9420

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.000742 AC: 49 AN: 66024

Other (OTH) AF: 0.0260 AC: 52 AN: 1998

Alfa AF: 0.00 Hom.: 293

ClinVar

Not reported in ClinVar

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;