dbSNP rs2236007: PAX9:c.631+41G>A (chr14-36663564-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372076.1(PAX9):c.631+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,609,186 control chromosomes in the GnomAD database, including 33,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2505 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30834 hom. )

Consequence

PAX9
NM_001372076.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.243

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]

PAX9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-36663564-G-A is Benign according to our data. Variant chr14-36663564-G-A is described in ClinVar as [Benign]. Clinvar id is 225820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_001372076.1 link	c.631+41G>A		intron_variant	Intron 2 of 3	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4 link	c.631+41G>A		intron_variant	Intron 3 of 4		NP_006185.1	P55771Q2L4T1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAX9	ENST00000361487.7 link	c.631+41G>A	intron_variant	Intron 2 of 3	1	NM_001372076.1	ENSP00000355245.6	P55771
PAX9	ENST00000402703.6 link	c.631+41G>A	intron_variant	Intron 3 of 4	5		ENSP00000384817.2	P55771
PAX9	ENST00000554201.1 link	n.950+41G>A	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24906

AN:

152050

Hom.:

2505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.182

AC:

42347

AN:

232420

Hom.:

4319

AF XY:

0.188

AC XY:

23987

AN XY:

127842

show subpopulations

Gnomad AFR exome

AF:

0.0692

Gnomad AMR exome

AF:

0.0950

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.202

AC:

293902

AN:

1457018

Hom.:

30834

Cov.:

AF XY:

0.202

AC XY:

146349

AN XY:

724752

show subpopulations

Gnomad4 AFR exome

AF:

0.0630

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.164

AC:

24909

AN:

152168

Hom.:

2505

Cov.:

AF XY:

0.163

AC XY:

12138

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0699

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.131

Hom.:

461

Bravo

AF:

0.159

Asia WGS

AF:

0.218

AC:

755

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypodontia

Benign:1

Jan 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over