14-36661915-G-C

Position:

chr14-36661915-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001372076.1(PAX9):c.-175G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 753,262 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 7 hom. )

Consequence

PAX9
NM_001372076.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.608

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 14-36661915-G-C is Benign according to our data. Variant chr14-36661915-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 883181.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00381 (581/152326) while in subpopulation AMR AF= 0.00647 (99/15310). AF 95% confidence interval is 0.00544. There are 4 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 581 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_001372076.1 linkuse as main transcript	c.-175G>C		5_prime_UTR_variant	1/4	ENST00000361487.7
PAX9	NM_006194.4 linkuse as main transcript	c.-175G>C		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
PAX9	ENST00000361487.7 linkuse as main transcript	c.-175G>C	5_prime_UTR_variant	1/4	1	NM_001372076.1	P1
PAX9	ENST00000402703.6 linkuse as main transcript	c.-175G>C	5_prime_UTR_variant	2/5	5		P1
PAX9	ENST00000555639.2 linkuse as main transcript	c.-79-96G>C	intron_variant		5
PAX9	ENST00000553267.4 linkuse as main transcript	n.552G>C	non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00647

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.00309

AC:

1857

AN:

600936

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

974

AN XY:

319300

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.0000550

Gnomad4 EAS exome

AF:

0.000375

Gnomad4 SAS exome

AF:

0.000750

Gnomad4 FIN exome

AF:

0.00246

Gnomad4 NFE exome

AF:

0.00382

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.00381

AC:

581

AN:

152326

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00382

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00328

Hom.:

Bravo

AF:

0.00406

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.44

CADD

Benign

DANN

Benign

0.84

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