chr14-36659731-G-T

Variant names:

• chr14-36659731-G-T
• rs2073241
• NM_006194.4:c.-394+1831G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006194.4(PAX9):​c.-394+1831G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,026 control chromosomes in the GnomAD database, including 8,614 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 0.33 (8614 hom., cov: 32)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 5 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	NM_006194.4		c.-394+1831G>T		intron	N/A	NP_006185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000402703.6	TSL:5	c.-394+1831G>T		intron	N/A	ENSP00000384817.2
	PAX9	ENST00000555639.2	TSL:5	c.-80+1838G>T		intron	N/A	ENSP00000501203.1
	PAX9	ENST00000553267.4	TSL:4	n.333+1831G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50170 AN: 151908 Hom.: 8611 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.330 AC: 50196 AN: 152026 Hom.: 8614 Cov.: 32 AF XY: 0.331 AC XY: 24556 AN XY: 74298

African (AFR) AF: 0.251 AC: 10393 AN: 41486

American (AMR) AF: 0.291 AC: 4451 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2322 AN: 5142

South Asian (SAS) AF: 0.415 AC: 1993 AN: 4808

European-Finnish (FIN) AF: 0.310 AC: 3269 AN: 10556

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25015 AN: 67974

Other (OTH) AF: 0.362 AC: 764 AN: 2108

Alfa AF: 0.361 Hom.: 37754

Bravo AF: 0.325

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2073241; hg19: chr14-37128936;