rs9979235

chr21-42736659-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.568+3233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,274 control chromosomes in the GnomAD database, including 1,751 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 (1751 hom., cov: 32)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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-AS1 (HGNC:40440): (PDE9A antisense RNA 1)

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 = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE9A	NM_002606.3	c.568+3233A>G		intron_variant		ENST00000291539.11
PDE9A-AS1	NR_183525.1	n.665-1977T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE9A	ENST00000291539.11	c.568+3233A>G		intron_variant		1	NM_002606.3
PDE9A-AS1	ENST00000437426.1	n.666-1977T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17112 AN: 152156 Hom.: 1741 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0990

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

GnomAD4 genome AF: 0.113 AC: 17170 AN: 152274 Hom.: 1751 Cov.: 32 AF XY: 0.112 AC XY: 8346 AN XY: 74460

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.0634

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0703 Hom.: 662

Bravo AF: 0.123

Asia WGS AF: 0.188 AC: 656 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	0.99
Dann	Benign	0.67

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: rs9979235; hg19: chr21-44156769;