rs2073247

chr14-36661540-C-T

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.-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

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=-0.74).
• BP6: Variant 14-36661540-C-T is Benign according to our data. Variant chr14-36661540-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_006194.4	c.-393-157C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000402703.6	c.-393-157C>T		intron_variant		5		P1
PAX9	ENST00000555639.2	c.-79-471C>T		intron_variant		5
PAX9	ENST00000553267.4	n.334-157C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.364

Alfa AF: 0.340 Hom.: 1092

Bravo AF: 0.326

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	3.8
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073247; hg19: chr14-37130745;