rs7559271

chr2-222203567-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181458.4(PAX3):c.1174-1377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,808 control chromosomes in the GnomAD database, including 23,248 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 0.54 (23248 hom., cov: 29)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

Genes affected

PAX3 (HGNC:8617): (paired box 3) This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. Mutations in paired box gene 3 are associated with Waardenburg syndrome, craniofacial-deafness-hand syndrome, and alveolar rhabdomyosarcoma. The translocation t(2;13)(q35;q14), which represents a fusion between PAX3 and the forkhead gene, is a frequent finding in alveolar rhabdomyosarcoma. Alternative splicing results in transcripts encoding isoforms with different C-termini. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.1174-1377C>T		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.1174-1377C>T		intron_variant		1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82477 AN: 151690 Hom.: 23232 Cov.: 29

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.544 AC: 82535 AN: 151808 Hom.: 23248 Cov.: 29 AF XY: 0.536 AC XY: 39793 AN XY: 74178

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.521

Alfa AF: 0.598 Hom.: 15693

Bravo AF: 0.524

Asia WGS AF: 0.470 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.69
Dann	Benign	0.38

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: rs7559271; hg19: chr2-223068286;