rs61734510

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000361487.7(PAX9):c.516G>A(p.Lys172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,613,250 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 86 hom. )

Consequence

PAX9
ENST00000361487.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.31

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-36663408-G-A is Benign according to our data. Variant chr14-36663408-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 313168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00937 (1427/152294) while in subpopulation AFR AF= 0.0145 (603/41570). AF 95% confidence interval is 0.0135. There are 13 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1427 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX9	NM_001372076.1 linkuse as main transcript	c.516G>A	p.Lys172=	synonymous_variant	2/4	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4 linkuse as main transcript	c.516G>A	p.Lys172=	synonymous_variant	3/5		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PAX9	ENST00000361487.7 linkuse as main transcript	c.516G>A	p.Lys172=	synonymous_variant	2/4	1	NM_001372076.1	ENSP00000355245	P1
PAX9	ENST00000402703.6 linkuse as main transcript	c.516G>A	p.Lys172=	synonymous_variant	3/5	5		ENSP00000384817	P1
PAX9	ENST00000554201.1 linkuse as main transcript	n.835G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00939

AC:

1429

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00892

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00675

AC:

1667

AN:

247088

Hom.:

AF XY:

0.00687

AC XY:

923

AN XY:

134256

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00906

Gnomad FIN exome

AF:

0.00390

Gnomad NFE exome

AF:

0.00788

Gnomad OTH exome

AF:

0.00924

GnomAD4 exome

AF:

0.00872

AC:

12735

AN:

1460956

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

6252

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00910

Gnomad4 FIN exome

AF:

0.00475

Gnomad4 NFE exome

AF:

0.00931

Gnomad4 OTH exome

AF:

0.00797

GnomAD4 genome

AF:

0.00937

AC:

1427

AN:

152294

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00633

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00892

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00767

Hom.:

Bravo

AF:

0.00972

EpiCase

AF:

0.00812

EpiControl

AF:

0.00788

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	PAX9: BP4, BS1, BS2 -

Partial congenital absence of teeth

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Tooth agenesis, selective, 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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