rs11847165

chr14-36677270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001372076.1(PAX9):c.*818C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,858 control chromosomes in the GnomAD database, including 3,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3021 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: PAX9 NM_001372076.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.862

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 14-36677270-C-T is Benign according to our data. Variant chr14-36677270-C-T is described in ClinVar as [Benign]. Clinvar id is 313183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_001372076.1	c.*818C>T		3_prime_UTR_variant	4/4	ENST00000361487.7
PAX9	NM_006194.4	c.*818C>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000361487.7	c.*818C>T		3_prime_UTR_variant	4/4	1	NM_001372076.1	P1
PAX9	ENST00000402703.6	c.*818C>T		3_prime_UTR_variant	5/5	5		P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28762 AN: 151660 Hom.: 3014 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.131 AC: 11 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.138 AC XY: 8 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0972

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.190 AC: 28800 AN: 151774 Hom.: 3021 Cov.: 32 AF XY: 0.196 AC XY: 14558 AN XY: 74146

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.189

Alfa AF: 0.166 Hom.: 2273

Bravo AF: 0.198

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Tooth agenesis, selective, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	15
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs11847165; hg19: chr14-37146475;