chr14-36669423-T-C

Variant names:

• chr14-36669423-T-C
• rs1955734
• NM_001372076.1:c.771+2822T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001372076.1(PAX9):​c.771+2822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,748 control chromosomes in the GnomAD database, including 19,723 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 0.48 (19723 hom., cov: 33)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_001372076.1	c.771+2822T>C		intron_variant	Intron 3 of 3	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4	c.771+2822T>C		intron_variant	Intron 4 of 4		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000361487.7	c.771+2822T>C		intron_variant	Intron 3 of 3	1	NM_001372076.1	ENSP00000355245.6
PAX9	ENST00000402703.6	c.771+2822T>C		intron_variant	Intron 4 of 4	5		ENSP00000384817.2
PAX9	ENST00000554201.1	n.1080+2832T>C		intron_variant	Intron 2 of 2	2
PAX9	ENST00000557107.1	n.613-1626T>C		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72701 AN: 151628 Hom.: 19722 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.600

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.479 AC: 72725 AN: 151748 Hom.: 19723 Cov.: 33 AF XY: 0.482 AC XY: 35744 AN XY: 74132

African (AFR) AF: 0.227 AC: 9396 AN: 41326

American (AMR) AF: 0.419 AC: 6393 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2248 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3895 AN: 5174

South Asian (SAS) AF: 0.698 AC: 3364 AN: 4820

European-Finnish (FIN) AF: 0.504 AC: 5303 AN: 10528

Middle Eastern (MID) AF: 0.603 AC: 175 AN: 290

European-Non Finnish (NFE) AF: 0.593 AC: 40249 AN: 67860

Other (OTH) AF: 0.527 AC: 1110 AN: 2108

Alfa AF: 0.571 Hom.: 36690

Bravo AF: 0.460

Asia WGS AF: 0.688 AC: 2384 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		2.3
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: rs1955734; hg19: chr14-37138628;