NM_000921.5:c.-6T>G

Variant names:

• chr12-20369279-T-G
• rs113972487
• NM_000921.5:c.-6T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000921.5(PDE3A):​c.-6T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,508,492 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (60 hom.)
• Consequence: PDE3A NM_000921.5 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.307
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-20369279-T-G is Benign according to our data. Variant chr12-20369279-T-G is described in ClinVar as Benign. ClinVar VariationId is 3037518.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 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.-6T>G		5_prime_UTR	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.-6T>G		5_prime_UTR	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-1034T>G		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.-6T>G		5_prime_UTR	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.-6T>G		5_prime_UTR	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+562A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2599 AN: 151886 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00390 AC: 452 AN: 115798 AF XY: 0.00323

Gnomad AFR exome AF: 0.0618

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000750

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.00172 AC: 2331 AN: 1356488 Hom.: 60 Cov.: 32 AF XY: 0.00149 AC XY: 987 AN XY: 663544

African (AFR) AF: 0.0633 AC: 1947 AN: 30750

American (AMR) AF: 0.00248 AC: 80 AN: 32272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22312

East Asian (EAS) AF: 0.00 AC: 0 AN: 35220

South Asian (SAS) AF: 0.000151 AC: 11 AN: 72908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45966

Middle Eastern (MID) AF: 0.00101 AC: 5 AN: 4932

European-Non Finnish (NFE) AF: 0.0000653 AC: 69 AN: 1056094

Other (OTH) AF: 0.00391 AC: 219 AN: 56034

GnomAD4 genome AF: 0.0171 AC: 2604 AN: 152004 Hom.: 84 Cov.: 32 AF XY: 0.0164 AC XY: 1221 AN XY: 74270

African (AFR) AF: 0.0600 AC: 2488 AN: 41498

American (AMR) AF: 0.00575 AC: 88 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67940

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00677 Hom.: 14

Bravo AF: 0.0195

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PDE3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		-0.31
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113972487; hg19: chr12-20522213;