NM_002606.3:c.70-6287A>C

Variant names:

• chr21-42679905-A-C
• rs3819902
• NM_002606.3:c.70-6287A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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 = 0.317 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE9A	NM_002606.3	MANE Select	c.70-6287A>C		intron	N/A	NP_002597.1	O76083-1
	PDE9A	NM_001001583.2		c.70-6287A>C		intron	N/A	NP_001001583.1	O76083-15
	PDE9A	NM_001001582.2		c.18-8012A>C		intron	N/A	NP_001001582.1	O76083-14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE9A	ENST00000291539.11	TSL:1 MANE Select	c.70-6287A>C		intron	N/A	ENSP00000291539.6	O76083-1
	PDE9A	ENST00000328862.10	TSL:1	c.70-6287A>C		intron	N/A	ENSP00000328699.6	O76083-15
	PDE9A	ENST00000398225.7	TSL:1	c.18-8012A>C		intron	N/A	ENSP00000381281.3	O76083-14

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

African (AFR) AF: 0.0945 AC: 3923 AN: 41528

American (AMR) AF: 0.0792 AC: 1212 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1702 AN: 5150

South Asian (SAS) AF: 0.151 AC: 727 AN: 4812

European-Finnish (FIN) AF: 0.101 AC: 1075 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7877 AN: 67994

Other (OTH) AF: 0.117 AC: 246 AN: 2108

Alfa AF: 0.116 Hom.: 2141

Bravo AF: 0.114

Asia WGS AF: 0.217 AC: 755 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	0.34
DANN	Benign	0.82
PhyloP100		-0.71
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: rs3819902; hg19: chr21-44100015;