14-36675402-A-T

Position:

• chr14-36675402-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001372076.1(PAX9):​c.772-796A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,198 control chromosomes in the GnomAD database, including 1,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1823 hom., cov: 33)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX9	NM_001372076.1	c.772-796A>T		intron_variant		ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4	c.772-796A>T		intron_variant			NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000361487.7	c.772-796A>T		intron_variant		1	NM_001372076.1	ENSP00000355245	P1
PAX9	ENST00000402703.6	c.772-796A>T		intron_variant		5		ENSP00000384817	P1
PAX9	ENST00000554201.1	n.1081-796A>T		intron_variant, non_coding_transcript_variant		2
PAX9	ENST00000557107.1	n.838-796A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20227 AN: 152078 Hom.: 1815 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.133 AC: 20267 AN: 152198 Hom.: 1823 Cov.: 33 AF XY: 0.139 AC XY: 10360 AN XY: 74392

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0640

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0385 Hom.: 40

Bravo AF: 0.149

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.81

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: rs7144276; hg19: chr14-37144607;