rs3819902

Positions:

• chr21-42679905-A-C
• chr21-42679905-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002606.3(PDE9A):​c.70-6287A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,158 control chromosomes in the GnomAD database, including 1,178 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1178 hom., cov: 33)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

PDE9A (HGNC:8795): (phosphodiesterase 9A) The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PDE9A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.70-6287A>C		intron_variant		ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.70-6287A>C		intron_variant		1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17480 AN: 152040 Hom.: 1181 Cov.: 33

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17476 AN: 152158 Hom.: 1178 Cov.: 33 AF XY: 0.116 AC XY: 8621 AN XY: 74380

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.117

Alfa AF: 0.114 Hom.: 1475

Bravo AF: 0.114

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs3819902; hg19: chr21-44100015;