rs2073247

Variant names:

• chr14-36661540-C-T
• rs2073247
• NM_006194.4:c.-393-157C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-36661540-C-T
• chr14-36661540-C-A

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.-393-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,168 control chromosomes in the GnomAD database, including 8,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8731 hom., cov: 33)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.835
• Publications: 13 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=-0.74).
• BP6: Variant 14-36661540-C-T is Benign according to our data. Variant chr14-36661540-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.-393-157C>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.-393-157C>T		intron	N/A	ENSP00000384817.2	P55771
	PAX9	ENST00000555639.2	TSL:5	c.-79-471C>T		intron	N/A	ENSP00000501203.1	A0A669KBA7
	PAX9	ENST00000553267.4	TSL:4	n.334-157C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50493 AN: 152048 Hom.: 8728 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.332 AC: 50519 AN: 152168 Hom.: 8731 Cov.: 33 AF XY: 0.333 AC XY: 24738 AN XY: 74376

African (AFR) AF: 0.251 AC: 10421 AN: 41532

American (AMR) AF: 0.294 AC: 4502 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1498 AN: 3472

East Asian (EAS) AF: 0.453 AC: 2333 AN: 5152

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3326 AN: 10590

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25169 AN: 67986

Other (OTH) AF: 0.364 AC: 770 AN: 2114

Alfa AF: 0.340 Hom.: 1092

Bravo AF: 0.326

Asia WGS AF: 0.415 AC: 1445 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	-0.74
CADD	Benign	3.8
DANN	Benign	0.88
PhyloP100		-0.83
PromoterAI		-0.0072	Neutral
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: rs2073247; hg19: chr14-37130745;