chr21-42754033-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002606.3(PDE9A):c.779C>T(p.Thr260Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PDE9A
NM_002606.3 missense
NM_002606.3 missense
Scores
2
12
3
Clinical Significance
Conservation
PhyloP100: 5.35
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE9A | NM_002606.3 | c.779C>T | p.Thr260Ile | missense_variant | 10/20 | ENST00000291539.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE9A | ENST00000291539.11 | c.779C>T | p.Thr260Ile | missense_variant | 10/20 | 1 | NM_002606.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152052Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251088Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135748
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461234Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726950
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152052Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74254
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 07, 2022 | The c.779C>T (p.T260I) alteration is located in exon 10 (coding exon 10) of the PDE9A gene. This alteration results from a C to T substitution at nucleotide position 779, causing the threonine (T) at amino acid position 260 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
P;P;P;P;P;P;P;D;D;P;P;P;P
Vest4
MutPred
0.38
.;Loss of phosphorylation at T260 (P = 0.0346);.;.;.;.;.;.;.;.;.;.;.;
MVP
MPC
0.71
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at