21-42688133-C-G

Position:

• chr21-42688133-C-G

Variant summary

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

The NM_002606.3(PDE9A):​c.218+139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 730,018 control chromosomes in the GnomAD database, including 10,552 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 0.15 (1948 hom., cov: 32)
  • Exomes 𝑓: 0.16 (8604 hom.)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.218+139C>G		intron_variant		ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.218+139C>G		intron_variant		1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23505 AN: 152064 Hom.: 1950 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.164 AC: 94642 AN: 577836 Hom.: 8604 AF XY: 0.164 AC XY: 50121 AN XY: 306306

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0840

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.155 AC: 23524 AN: 152182 Hom.: 1948 Cov.: 32 AF XY: 0.154 AC XY: 11471 AN XY: 74406

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0661 Hom.: 75

Bravo AF: 0.155

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13047947; hg19: chr21-44108243;