rs13047947

Variant names:

• chr21-42688133-C-A
• rs13047947
• NM_002606.3:c.218+139C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-42688133-C-A
• chr21-42688133-C-G
• chr21-42688133-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002606.3(PDE9A):​c.218+139C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 730,428 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.218+139C>A		intron_variant	Intron 3 of 19	ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.218+139C>A		intron_variant	Intron 3 of 19	1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000242 AC: 14 AN: 578336 Hom.: 0 AF XY: 0.0000228 AC XY: 7 AN XY: 306560

African (AFR) AF: 0.0000614 AC: 1 AN: 16288

American (AMR) AF: 0.00 AC: 0 AN: 33002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18238

East Asian (EAS) AF: 0.00 AC: 0 AN: 32022

South Asian (SAS) AF: 0.00 AC: 0 AN: 59970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3992

European-Non Finnish (NFE) AF: 0.0000314 AC: 11 AN: 350668

Other (OTH) AF: 0.0000642 AC: 2 AN: 31130

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74290

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 75

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13047947; hg19: chr21-44108243;