NM_000921.5:c.-95_-92dupCGTG

Variant names:

• chr12-20369180-A-AGCGT
• rs71039938
• NM_000921.5:c.-95_-92dupCGTG

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.184
• 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 12-20369180-A-AGCGT is Benign according to our data. Variant chr12-20369180-A-AGCGT is described in ClinVar as Benign. ClinVar VariationId 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.

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.-95_-92dupCGTG		5_prime_UTR	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.-95_-92dupCGTG		5_prime_UTR	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-1123_-1120dupCGTG		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.-95_-92dupCGTG		5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.-95_-92dupCGTG		5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+657_422+660dupACGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.259 AC: 32398 AN: 125132 Hom.: 4446 Cov.: 22

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

African (AFR) AF: 0.0489 AC: 683 AN: 13962

American (AMR) AF: 0.184 AC: 3127 AN: 16960

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 2562 AN: 13138

East Asian (EAS) AF: 0.0341 AC: 1032 AN: 30228

South Asian (SAS) AF: 0.168 AC: 6350 AN: 37894

European-Finnish (FIN) AF: 0.187 AC: 5787 AN: 30954

Middle Eastern (MID) AF: 0.239 AC: 482 AN: 2014

European-Non Finnish (NFE) AF: 0.227 AC: 73249 AN: 322436

Other (OTH) AF: 0.205 AC: 5524 AN: 26958

GnomAD4 genome AF: 0.259 AC: 32388 AN: 125232 Hom.: 4443 Cov.: 22 AF XY: 0.251 AC XY: 15240 AN XY: 60624

African (AFR) AF: 0.0961 AC: 2703 AN: 28116

American (AMR) AF: 0.255 AC: 3533 AN: 13874

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 820 AN: 3078

East Asian (EAS) AF: 0.0643 AC: 267 AN: 4154

South Asian (SAS) AF: 0.254 AC: 996 AN: 3922

European-Finnish (FIN) AF: 0.257 AC: 2072 AN: 8060

Middle Eastern (MID) AF: 0.374 AC: 98 AN: 262

European-Non Finnish (NFE) AF: 0.344 AC: 21032 AN: 61178

Other (OTH) AF: 0.268 AC: 474 AN: 1770

Alfa AF: 0.0922 Hom.: 149

ClinVar

ClinVar submissions as Germline

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		0.18

Splicing

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

Other links and lift over

dbSNP: rs71039938; hg19: chr12-20522114;