14-36661872-G-T

Variant names:

• chr14-36661872-G-T
• rs533579629
• NM_001372076.1:c.-218G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001372076.1(PAX9):​c.-218G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 638,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: PAX9 NM_001372076.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 0 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000853 (13/152326) while in subpopulation AFR AF = 0.000289 (12/41576). AF 95% confidence interval is 0.000166. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372076.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	NM_001372076.1	MANE Select	c.-218G>T		5_prime_UTR	Exon 1 of 4	NP_001359005.1	P55771
	PAX9	NM_006194.4		c.-218G>T		5_prime_UTR	Exon 2 of 5	NP_006185.1	P55771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000361487.7	TSL:1 MANE Select	c.-218G>T		5_prime_UTR	Exon 1 of 4	ENSP00000355245.6	P55771
	PAX9	ENST00000402703.6	TSL:5	c.-218G>T		5_prime_UTR	Exon 2 of 5	ENSP00000384817.2	P55771
	PAX9	ENST00000555639.2	TSL:5	c.-79-139G>T		intron	N/A	ENSP00000501203.1	A0A669KBA7

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000308 AC: 15 AN: 486462 Hom.: 0 Cov.: 5 AF XY: 0.0000310 AC XY: 8 AN XY: 257846

African (AFR) AF: 0.000147 AC: 2 AN: 13584

American (AMR) AF: 0.0000387 AC: 1 AN: 25816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15046

East Asian (EAS) AF: 0.00 AC: 0 AN: 30886

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 49942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33106

Middle Eastern (MID) AF: 0.000482 AC: 1 AN: 2074

European-Non Finnish (NFE) AF: 0.0000312 AC: 9 AN: 288700

Other (OTH) AF: 0.0000366 AC: 1 AN: 27308

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74482

African (AFR) AF: 0.000289 AC: 12 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.90
PhyloP100		3.0
PromoterAI		-0.066	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs533579629; hg19: chr14-37131077;