rs767731909

Variant names:

• chr21-42686229-T-C
• rs767731909
• NM_002606.3:c.107T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-42686229-T-C
• chr21-42686229-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002606.3(PDE9A):​c.107T>C​(p.Met36Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M36R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDE9A NM_002606.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41304865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.107T>C	p.Met36Thr	missense_variant	Exon 2 of 20	ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.107T>C	p.Met36Thr	missense_variant	Exon 2 of 20	1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	.;T;.;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.86	D;D;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.6	L;L;L;L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.48	P;P;B;P;P
Vest4		0.66
MutPred		0.40		Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP		0.76
MPC		0.42
ClinPred		0.75	D
GERP RS		4.9
Varity_R		0.14
gMVP		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: rs767731909; hg19: chr21-44106339;