14-36657839-C-G

Variant names:

• chr14-36657839-C-G
• rs4904155
• NM_006194.4:c.-455C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006194.4(PAX9):​c.-455C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,094 control chromosomes in the GnomAD database, including 10,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10671 hom., cov: 32)
  • Exomes 𝑓: 0.32 (15 hom.)
• Consequence: PAX9 NM_006194.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• 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 -16 ACMG points.

• BP6: Variant 14-36657839-C-G is Benign according to our data. Variant chr14-36657839-C-G is described in ClinVar as Benign. ClinVar VariationId is 313155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 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.-455C>G		5_prime_UTR	Exon 1 of 5	NP_006185.1	P55771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000402703.6	TSL:5	c.-455C>G		5_prime_UTR	Exon 1 of 5	ENSP00000384817.2	P55771
	PAX9	ENST00000555639.2	TSL:5	c.-134C>G		5_prime_UTR	Exon 1 of 3	ENSP00000501203.1	A0A669KBA7
	PAX9	ENST00000553267.4	TSL:4	n.272C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56439 AN: 151806 Hom.: 10657 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.324 AC: 55 AN: 170 Hom.: 15 Cov.: 0 AF XY: 0.341 AC XY: 45 AN XY: 132

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.324 AC: 44 AN: 136

Other (OTH) AF: 0.250 AC: 3 AN: 12

GnomAD4 genome AF: 0.372 AC: 56490 AN: 151924 Hom.: 10671 Cov.: 32 AF XY: 0.372 AC XY: 27623 AN XY: 74266

African (AFR) AF: 0.395 AC: 16372 AN: 41440

American (AMR) AF: 0.307 AC: 4688 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2308 AN: 5122

South Asian (SAS) AF: 0.414 AC: 1989 AN: 4802

European-Finnish (FIN) AF: 0.310 AC: 3281 AN: 10586

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

European-Non Finnish (NFE) AF: 0.368 AC: 25016 AN: 67926

Other (OTH) AF: 0.392 AC: 820 AN: 2092

Alfa AF: 0.364 Hom.: 1322

Bravo AF: 0.373

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.45
PhyloP100		-1.1
PromoterAI		-0.026	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4904155; hg19: chr14-37127044;