rs4904210

chr14-36666548-G-Achr14-36666548-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001372076.1(PAX9):c.718G>A(p.Ala240Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A240P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAX9 NM_001372076.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25183743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX9	NM_001372076.1	c.718G>A	p.Ala240Thr	missense_variant	3/4	ENST00000361487.7
PAX9	NM_006194.4	c.718G>A	p.Ala240Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX9	ENST00000361487.7	c.718G>A	p.Ala240Thr	missense_variant	3/4	1	NM_001372076.1	P1
PAX9	ENST00000402703.6	c.718G>A	p.Ala240Thr	missense_variant	4/5	5		P1
PAX9	ENST00000554201.1	n.1037G>A		non_coding_transcript_exon_variant	2/3	2
PAX9	ENST00000557107.1	n.559G>A		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1433202 Hom.: 0 Cov.: 54 AF XY: 0.00 AC XY: 0 AN XY: 710138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	T;.;T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.64	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.056	B;B;.
Vest4		0.18
MutPred		0.35		Gain of phosphorylation at A240 (P = 0.0417);Gain of phosphorylation at A240 (P = 0.0417);.;
MVP		0.74
MPC		0.27
ClinPred		0.18	T
GERP RS		3.4
Varity_R		0.075
gMVP		0.18

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: rs4904210; hg19: chr14-37135753;