rs61734510

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001372076.1(PAX9):c.516G>A(p.Lys172Lys) 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
NM_001372076.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.31

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

tooth agenesis, selective, 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PAX9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1427 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_001372076.1 link	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 2 of 4	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4 link	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 3 of 5		NP_006185.1	P55771Q2L4T1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAX9	ENST00000361487.7 link	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 2 of 4	1	NM_001372076.1	ENSP00000355245.6	P55771
PAX9	ENST00000402703.6 link	c.516G>A	p.Lys172Lys	synonymous_variant	Exon 3 of 5	5		ENSP00000384817.2	P55771
PAX9	ENST00000554201.1 link	n.835G>A		non_coding_transcript_exon_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.00675

AC:

1667

AN:

247088

AF XY:

0.00687

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 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

African (AFR)

AF:

0.0185

AC:

618

AN:

33476

American (AMR)

AF:

0.00389

AC:

174

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00910

AC:

785

AN:

86236

European-Finnish (FIN)

AF:

0.00475

AC:

251

AN:

52814

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00931

AC:

10347

AN:

1111790

Other (OTH)

AF:

0.00797

AC:

481

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

826

1651

2477

3302

4128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00937

AC:

1427

AN:

152294

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0145

AC:

603

AN:

41570

American (AMR)

AF:

0.00633

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.000389

AC:

AN:

5144

South Asian (SAS)

AF:

0.00725

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00892

AC:

607

AN:

68032

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

150

226

301

376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00775

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PAX9: BP4, BS1, BS2 -

Tooth agenesis, selective, 3

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Hypodontia

Benign:1

Dec 19, 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

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

2.3

Mutation Taster

=287/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over