rs17176643

chr14-36673764-C-Achr14-36673764-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
PAX9	NM_001372076.1	c.772-2434C>A		intron_variant		ENST00000361487.7
PAX9	NM_006194.4	c.772-2434C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000361487.7	c.772-2434C>A		intron_variant		1	NM_001372076.1	P1
PAX9	ENST00000402703.6	c.772-2434C>A		intron_variant		5		P1
PAX9	ENST00000554201.1	n.1081-2434C>A		intron_variant, non_coding_transcript_variant		2
PAX9	ENST00000557107.1	n.837+1655C>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.317

Alfa AF: 0.333 Hom.: 11190

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

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: rs17176643; hg19: chr14-37142969;