14-36660788-C-T

Variant names:

• chr14-36660788-C-T
• rs2073246
• NM_006194.4:c.-393-909C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006194.4(PAX9):​c.-393-909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,166 control chromosomes in the GnomAD database, including 8,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8117 hom., cov: 33)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.281
• Publications: 7 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

ENSG00000258661 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-36660788-C-T is Benign according to our data. Variant chr14-36660788-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	NM_006194.4		c.-393-909C>T		intron	N/A	NP_006185.1	P55771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000402703.6	TSL:5	c.-393-909C>T		intron	N/A	ENSP00000384817.2	P55771
	PAX9	ENST00000555639.2	TSL:5	c.-79-1223C>T		intron	N/A	ENSP00000501203.1	A0A669KBA7
	PAX9	ENST00000553267.4	TSL:4	n.334-909C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48101 AN: 152048 Hom.: 8111 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.316 AC: 48125 AN: 152166 Hom.: 8117 Cov.: 33 AF XY: 0.317 AC XY: 23598 AN XY: 74388

African (AFR) AF: 0.204 AC: 8457 AN: 41514

American (AMR) AF: 0.285 AC: 4363 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2338 AN: 5174

South Asian (SAS) AF: 0.415 AC: 2004 AN: 4824

European-Finnish (FIN) AF: 0.311 AC: 3288 AN: 10584

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24969 AN: 67994

Other (OTH) AF: 0.349 AC: 737 AN: 2112

Alfa AF: 0.358 Hom.: 5166

Bravo AF: 0.308

Asia WGS AF: 0.410 AC: 1429 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-0.28
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: rs2073246; hg19: chr14-37129993;