14-36659359-C-A

Position:

• chr14-36659359-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006194.4(PAX9):​c.-394+1459C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,138 control chromosomes in the GnomAD database, including 2,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2432 hom., cov: 33)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-36659359-C-A is Benign according to our data. Variant chr14-36659359-C-A is described in ClinVar as [Benign]. Clinvar id is 1597367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_006194.4	c.-394+1459C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000402703.6	c.-394+1459C>A		intron_variant		5		P1
PAX9	ENST00000555639.2	c.-80+1466C>A		intron_variant		5
PAX9	ENST00000553267.4	n.333+1459C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23731 AN: 152020 Hom.: 2432 Cov.: 33

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.156 AC: 23735 AN: 152138 Hom.: 2432 Cov.: 33 AF XY: 0.156 AC XY: 11570 AN XY: 74374

Gnomad4 AFR AF: 0.0453

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.171

Alfa AF: 0.195 Hom.: 716

Bravo AF: 0.150

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Partial congenital absence of teeth Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34914085; hg19: chr14-37128564;