rs1555316697
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001372076.1(PAX9):c.59C>T(p.Pro20Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
PAX9
NM_001372076.1 missense
NM_001372076.1 missense
Scores
17
1
1
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
PAX9 (HGNC:8623): (paired box 9) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. Mice lacking this gene exhibit impaired development of organs, musculature and the skeleton, including absent and abnormally developed teeth, and neonatal lethality. Mutations in the human gene are associated with selective tooth agenesis-3. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 1 uncertain in NM_001372076.1
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
?
Variant 14-36662951-C-T is Pathogenic according to our data. Variant chr14-36662951-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375454.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAX9 | NM_001372076.1 | c.59C>T | p.Pro20Leu | missense_variant | 2/4 | ENST00000361487.7 | |
PAX9 | NM_006194.4 | c.59C>T | p.Pro20Leu | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAX9 | ENST00000361487.7 | c.59C>T | p.Pro20Leu | missense_variant | 2/4 | 1 | NM_001372076.1 | P1 | |
PAX9 | ENST00000402703.6 | c.59C>T | p.Pro20Leu | missense_variant | 3/5 | 5 | P1 | ||
PAX9 | ENST00000555639.2 | c.59C>T | p.Pro20Leu | missense_variant | 3/3 | 5 | |||
PAX9 | ENST00000554201.1 | n.378C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Tooth agenesis, selective, 3 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University | - | - - |
Pathogenic, no assertion criteria provided | research | Maesawa Lab, Iwate Medical University | Jan 18, 2017 | The variant co-segregates with tooth agenesis in a family (3 affected, 1 unaffected). The Polyphen-2 score is 1.0 (probably damaging). In vitro experiment confirmed a functional defect of the variant protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);
MVP
MPC
3.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at