chr14-36671299-C-T

Variant names:

• chr14-36671299-C-T
• rs8004187
• NM_001372076.1:c.771+4698C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372076.1(PAX9):​c.771+4698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,874 control chromosomes in the GnomAD database, including 24,117 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24117 hom., cov: 32)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 5 publications found

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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372076.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	NM_001372076.1	MANE Select	c.771+4698C>T		intron	N/A	NP_001359005.1	P55771
	PAX9	NM_006194.4		c.771+4698C>T		intron	N/A	NP_006185.1	P55771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000361487.7	TSL:1 MANE Select	c.771+4698C>T		intron	N/A	ENSP00000355245.6	P55771
	PAX9	ENST00000402703.6	TSL:5	c.771+4698C>T		intron	N/A	ENSP00000384817.2	P55771
	PAX9	ENST00000554201.1	TSL:2	n.1080+4708C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83527 AN: 151756 Hom.: 24112 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.581

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83562 AN: 151874 Hom.: 24117 Cov.: 32 AF XY: 0.550 AC XY: 40848 AN XY: 74246

African (AFR) AF: 0.396 AC: 16421 AN: 41448

American (AMR) AF: 0.457 AC: 6985 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2353 AN: 3466

East Asian (EAS) AF: 0.754 AC: 3899 AN: 5170

South Asian (SAS) AF: 0.719 AC: 3466 AN: 4822

European-Finnish (FIN) AF: 0.540 AC: 5703 AN: 10570

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42692 AN: 67814

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.599 Hom.: 13088

Bravo AF: 0.536

Asia WGS AF: 0.709 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8004187; hg19: chr14-37140504;