14-36662090-A-G

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5

The NM_001372076.1(PAX9):ā€‹c.1A>Gā€‹(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PAX9
NM_001372076.1 start_lost

Scores

7
6
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 13 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_001372076.1 (PAX9) was described as [Pathogenic] in ClinVar as 430692
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-36662090-A-G is Pathogenic according to our data. Variant chr14-36662090-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 13777.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PAX9NM_001372076.1 linkuse as main transcriptc.1A>G p.Met1? start_lost 1/4 ENST00000361487.7
PAX9NM_006194.4 linkuse as main transcriptc.1A>G p.Met1? start_lost 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PAX9ENST00000361487.7 linkuse as main transcriptc.1A>G p.Met1? start_lost 1/41 NM_001372076.1 P1
PAX9ENST00000402703.6 linkuse as main transcriptc.1A>G p.Met1? start_lost 2/55 P1
PAX9ENST00000555639.2 linkuse as main transcriptc.1A>G p.Met1? start_lost 2/35

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1169392
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
574120
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Tooth agenesis, selective, 3 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2005- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.50
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;.
M_CAP
Pathogenic
0.95
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
0.90
D
MutationTaster
Benign
1.0
D;D
PROVEAN
Benign
-1.4
N;N
REVEL
Pathogenic
0.67
Sift
Uncertain
0.018
D;D
Sift4G
Uncertain
0.038
D;D
Polyphen
0.14
B;B
Vest4
0.91
MutPred
0.99
Loss of disorder (P = 0.1886);Loss of disorder (P = 0.1886);
MVP
0.99
ClinPred
0.93
D
GERP RS
5.9
Varity_R
0.46
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-37131295; API