14-36671299-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.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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_001372076.1	c.771+4698C>T		intron_variant		ENST00000361487.7
PAX9	NM_006194.4	c.771+4698C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000361487.7	c.771+4698C>T		intron_variant		1	NM_001372076.1	P1
PAX9	ENST00000402703.6	c.771+4698C>T		intron_variant		5		P1
PAX9	ENST00000554201.1	n.1080+4708C>T		intron_variant, non_coding_transcript_variant		2
PAX9	ENST00000557107.1	n.707+156C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.583

Alfa AF: 0.583 Hom.: 7132

Bravo AF: 0.536

Asia WGS AF: 0.709 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.5
Dann	Benign	0.65

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: rs8004187; hg19: chr14-37140504;