rs778899140
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_001385079.1(PDE10A):āc.1118A>Gā(p.Tyr373Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
PDE10A
NM_001385079.1 missense
NM_001385079.1 missense
Scores
4
8
2
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PDE10A
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.8
PP5
?
Variant 6-165450268-T-C is Pathogenic according to our data. Variant chr6-165450268-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225633.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-165450268-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE10A | NM_001385079.1 | c.1118A>G | p.Tyr373Cys | missense_variant | 4/22 | ENST00000539869.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE10A | ENST00000539869.4 | c.1118A>G | p.Tyr373Cys | missense_variant | 4/22 | 1 | NM_001385079.1 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134802
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1454546Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 723442
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
ExAC
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Infantile-onset generalized dyskinesia with orofacial involvement Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 29, 2016 | - - |
Global developmental delay;C1858120:Generalized hypotonia Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Polyphen
1.0
.;.;.;.;.;D
MutPred
0.51
.;.;.;.;.;Gain of catalytic residue at S101 (P = 0.0643);
MVP
MPC
2.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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