rs61734510

Variant names:

• chr14-36663408-G-A
• rs61734510
• NM_001372076.1:c.516G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-36663408-G-A
• chr14-36663408-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001372076.1(PAX9):​c.516G>A​(p.Lys172Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,613,250 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (86 hom.)
• Consequence: PAX9 NM_001372076.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.31
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 14-36663408-G-A is Benign according to our data. Variant chr14-36663408-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 313168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00937 (1427/152294) while in subpopulation AFR AF = 0.0145 (603/41570). AF 95% confidence interval is 0.0135. There are 13 homozygotes in GnomAd4. There are 631 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1427 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.516G>A	p.Lys172Lys	synonymous	Exon 2 of 4	NP_001359005.1	P55771
	PAX9	NM_006194.4		c.516G>A	p.Lys172Lys	synonymous	Exon 3 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.516G>A	p.Lys172Lys	synonymous	Exon 2 of 4	ENSP00000355245.6	P55771
	PAX9	ENST00000402703.6	TSL:5	c.516G>A	p.Lys172Lys	synonymous	Exon 3 of 5	ENSP00000384817.2	P55771
	PAX9	ENST00000554201.1	TSL:2	n.835G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00939 AC: 1429 AN: 152176 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.00634

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00892

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00675 AC: 1667 AN: 247088 AF XY: 0.00687

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00390

Gnomad NFE exome AF: 0.00788

Gnomad OTH exome AF: 0.00924

GnomAD4 exome AF: 0.00872 AC: 12735 AN: 1460956 Hom.: 86 Cov.: 37 AF XY: 0.00860 AC XY: 6252 AN XY: 726784

African (AFR) AF: 0.0185 AC: 618 AN: 33476

American (AMR) AF: 0.00389 AC: 174 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00910 AC: 785 AN: 86236

European-Finnish (FIN) AF: 0.00475 AC: 251 AN: 52814

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5766

European-Non Finnish (NFE) AF: 0.00931 AC: 10347 AN: 1111790

Other (OTH) AF: 0.00797 AC: 481 AN: 60374

GnomAD4 genome AF: 0.00937 AC: 1427 AN: 152294 Hom.: 13 Cov.: 33 AF XY: 0.00848 AC XY: 631 AN XY: 74448

African (AFR) AF: 0.0145 AC: 603 AN: 41570

American (AMR) AF: 0.00633 AC: 97 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5144

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4826

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00892 AC: 607 AN: 68032

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00775 Hom.: 2

Bravo AF: 0.00972

EpiCase AF: 0.00812

EpiControl AF: 0.00788

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypodontia (1)
-	-	1	Tooth agenesis, selective, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		2.3
Mutation Taster		=287/13	polymorphism

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: rs61734510; hg19: chr14-37132613;