rs2073242

Positions:

• chr14-36660136-A-C
• chr14-36660136-A-G
• chr14-36660136-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006194.4(PAX9):​c.-393-1561A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,930 control chromosomes in the GnomAD database, including 27,442 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 0.60 (27442 hom., cov: 31)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_006194.4	c.-393-1561A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000402703.6	c.-393-1561A>C		intron_variant		5		P1
PAX9	ENST00000555639.2	c.-79-1875A>C		intron_variant		5
PAX9	ENST00000553267.4	n.334-1561A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90665 AN: 151812 Hom.: 27419 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.597 AC: 90731 AN: 151930 Hom.: 27442 Cov.: 31 AF XY: 0.594 AC XY: 44141 AN XY: 74280

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.617

Alfa AF: 0.617 Hom.: 43953

Bravo AF: 0.596

Asia WGS AF: 0.658 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.42

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: rs2073242; hg19: chr14-37129341;