rs17176643

Variant names:

• chr14-36673764-C-A
• rs17176643
• NM_001372076.1:c.772-2434C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-36673764-C-A
• chr14-36673764-C-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.772-2434C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,084 control chromosomes in the GnomAD database, including 8,198 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 0.30 (8198 hom., cov: 33)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_001372076.1	c.772-2434C>A		intron_variant	Intron 3 of 3	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4	c.772-2434C>A		intron_variant	Intron 4 of 4		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000361487.7	c.772-2434C>A		intron_variant	Intron 3 of 3	1	NM_001372076.1	ENSP00000355245.6
PAX9	ENST00000402703.6	c.772-2434C>A		intron_variant	Intron 4 of 4	5		ENSP00000384817.2
PAX9	ENST00000554201.1	n.1081-2434C>A		intron_variant	Intron 2 of 2	2
PAX9	ENST00000557107.1	n.837+1655C>A		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45729 AN: 151966 Hom.: 8192 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.301 AC: 45748 AN: 152084 Hom.: 8198 Cov.: 33 AF XY: 0.309 AC XY: 22995 AN XY: 74316

African (AFR) AF: 0.109 AC: 4523 AN: 41548

American (AMR) AF: 0.486 AC: 7425 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3462

East Asian (EAS) AF: 0.454 AC: 2348 AN: 5172

South Asian (SAS) AF: 0.350 AC: 1683 AN: 4812

European-Finnish (FIN) AF: 0.405 AC: 4269 AN: 10536

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23197 AN: 67964

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.332 Hom.: 14901

Bravo AF: 0.301

Asia WGS AF: 0.409 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.11
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: rs17176643; hg19: chr14-37142969;