14-36668175-A-G

Variant names:

• chr14-36668175-A-G
• rs12892031
• NM_001372076.1:c.771+1574A>G

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+1574A>G 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 151,950 control chromosomes in the GnomAD database, including 24,141 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 (24141 hom., cov: 32)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 2 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: 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=-0.87).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	NM_001372076.1	MANE Select	c.771+1574A>G		intron	N/A	NP_001359005.1
	PAX9	NM_006194.4		c.771+1574A>G		intron	N/A	NP_006185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000361487.7	TSL:1 MANE Select	c.771+1574A>G		intron	N/A	ENSP00000355245.6
	PAX9	ENST00000402703.6	TSL:5	c.771+1574A>G		intron	N/A	ENSP00000384817.2
	PAX9	ENST00000554201.1	TSL:2	n.1080+1584A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83590 AN: 151832 Hom.: 24136 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.539

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: 83625 AN: 151950 Hom.: 24141 Cov.: 32 AF XY: 0.550 AC XY: 40840 AN XY: 74250

African (AFR) AF: 0.396 AC: 16432 AN: 41460

American (AMR) AF: 0.458 AC: 6988 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3468

East Asian (EAS) AF: 0.754 AC: 3891 AN: 5162

South Asian (SAS) AF: 0.719 AC: 3464 AN: 4820

European-Finnish (FIN) AF: 0.539 AC: 5671 AN: 10524

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

European-Non Finnish (NFE) AF: 0.630 AC: 42782 AN: 67930

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

Alfa AF: 0.575 Hom.: 3181

Bravo AF: 0.536

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		0.30
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: rs12892031; hg19: chr14-37137380;