14-36660136-A-C

Variant names:

• chr14-36660136-A-C
• rs2073242
• NM_006194.4:c.-393-1561A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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

ENSG00000258661 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAX9	NM_006194.4	c.-393-1561A>C		intron_variant	Intron 1 of 4		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000402703.6	c.-393-1561A>C		intron_variant	Intron 1 of 4	5		ENSP00000384817.2
PAX9	ENST00000555639.2	c.-79-1875A>C		intron_variant	Intron 1 of 2	5		ENSP00000501203.1
PAX9	ENST00000553267.4	n.334-1561A>C		intron_variant	Intron 1 of 1	4
ENSG00000258661	ENST00000729136.1	n.534+717T>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.599 AC: 24801 AN: 41432

American (AMR) AF: 0.477 AC: 7275 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3855 AN: 5140

South Asian (SAS) AF: 0.605 AC: 2911 AN: 4810

European-Finnish (FIN) AF: 0.522 AC: 5507 AN: 10540

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.619 AC: 42089 AN: 67964

Other (OTH) AF: 0.617 AC: 1301 AN: 2110

Alfa AF: 0.612 Hom.: 75264

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
PhyloP100		-0.21
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: rs2073242; hg19: chr14-37129341;