chr21-42736659-A-G

Variant names:

• chr21-42736659-A-G
• rs9979235
• NM_002606.3:c.568+3233A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002606.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE9A	NM_002606.3	MANE Select	c.568+3233A>G		intron	N/A	NP_002597.1
	PDE9A	NM_001001583.2		c.490+3233A>G		intron	N/A	NP_001001583.1
	PDE9A	NM_001001582.2		c.445+3233A>G		intron	N/A	NP_001001582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE9A	ENST00000291539.11	TSL:1 MANE Select	c.568+3233A>G		intron	N/A	ENSP00000291539.6
	PDE9A	ENST00000328862.10	TSL:1	c.490+3233A>G		intron	N/A	ENSP00000328699.6
	PDE9A	ENST00000398225.7	TSL:1	c.445+3233A>G		intron	N/A	ENSP00000381281.3

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

African (AFR) AF: 0.236 AC: 9818 AN: 41542

American (AMR) AF: 0.0634 AC: 970 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1937 AN: 5182

South Asian (SAS) AF: 0.0469 AC: 226 AN: 4822

European-Finnish (FIN) AF: 0.0284 AC: 302 AN: 10618

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0480 AC: 3264 AN: 68028

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.0794 Hom.: 2283

Bravo AF: 0.123

Asia WGS AF: 0.188 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.67
PhyloP100		-0.050
Mutation Taster		=100/0	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: rs9979235; hg19: chr21-44156769;