rs79716763

Variant names:

• chr12-20369515-G-A
• rs79716763
• NM_000921.5:c.231G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-20369515-G-A
• chr12-20369515-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000921.5(PDE3A):​c.231G>A​(p.Leu77Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,560,594 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (23 hom.)
• Consequence: PDE3A NM_000921.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.26
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 12-20369515-G-A is Benign according to our data. Variant chr12-20369515-G-A is described in ClinVar as Benign. ClinVar VariationId is 717258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00872 (1328/152332) while in subpopulation AFR AF = 0.0304 (1263/41584). AF 95% confidence interval is 0.029. There are 21 homozygotes in GnomAd4. There are 630 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1328 AD gene.

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.231G>A	p.Leu77Leu	synonymous	Exon 1 of 16	NP_000912.3
	PDE3A	NM_001378407.1		c.231G>A	p.Leu77Leu	synonymous	Exon 1 of 14	NP_001365336.1
	PDE3A	NM_001378408.1		c.-798G>A		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.231G>A	p.Leu77Leu	synonymous	Exon 1 of 16	ENSP00000351957.3	Q14432
	PDE3A	ENST00000951762.1		c.231G>A	p.Leu77Leu	synonymous	Exon 1 of 15	ENSP00000621821.1
	PDE3A-AS1	ENST00000535755.1	TSL:4	n.422+326C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00872 AC: 1327 AN: 152214 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00199 AC: 326 AN: 164168 AF XY: 0.00151

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000890

GnomAD4 exome AF: 0.000842 AC: 1186 AN: 1408262 Hom.: 23 Cov.: 34 AF XY: 0.000721 AC XY: 501 AN XY: 695314

African (AFR) AF: 0.0302 AC: 971 AN: 32134

American (AMR) AF: 0.00147 AC: 55 AN: 37420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 36796

South Asian (SAS) AF: 0.000138 AC: 11 AN: 79978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48542

Middle Eastern (MID) AF: 0.00124 AC: 7 AN: 5660

European-Non Finnish (NFE) AF: 0.0000304 AC: 33 AN: 1084278

Other (OTH) AF: 0.00187 AC: 109 AN: 58350

GnomAD4 genome AF: 0.00872 AC: 1328 AN: 152332 Hom.: 21 Cov.: 32 AF XY: 0.00846 AC XY: 630 AN XY: 74496

African (AFR) AF: 0.0304 AC: 1263 AN: 41584

American (AMR) AF: 0.00307 AC: 47 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00125 Hom.: 1

Bravo AF: 0.00920

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79716763; hg19: chr12-20522449;