2-222201034-T-TAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181458.4(PAX3):c.*373_*374insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 793,502 control chromosomes in the GnomAD database, including 581 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (553 hom., cov: 31)
  • Exomes 𝑓: 0.0095 (28 hom.)
• Consequence: PAX3 NM_181458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -10 ACMG points.

• BP6: Variant 2-222201034-T-TAC is Benign according to our data. Variant chr2-222201034-T-TAC is described in ClinVar as [Benign]. Clinvar id is 1291395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.*373_*374insGT		3_prime_UTR_variant	9/9	ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.*373_*374insGT		3_prime_UTR_variant	9/9	1	NM_181458.4	A1
PAX3	ENST00000392069.6	c.*139_*140insGT		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7641 AN: 149178 Hom.: 554 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0304

Gnomad EAS AF: 0.00255

Gnomad SAS AF: 0.00235

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.0472

GnomAD4 exome AF: 0.00946 AC: 6096 AN: 644230 Hom.: 28 Cov.: 2 AF XY: 0.00842 AC XY: 2805 AN XY: 333214

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0280

Gnomad4 EAS exome AF: 0.00190

Gnomad4 SAS exome AF: 0.00227

Gnomad4 FIN exome AF: 0.00402

Gnomad4 NFE exome AF: 0.00408

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0513 AC: 7658 AN: 149272 Hom.: 553 Cov.: 31 AF XY: 0.0491 AC XY: 3573 AN XY: 72778

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0304

Gnomad4 EAS AF: 0.00236

Gnomad4 SAS AF: 0.00214

Gnomad4 FIN AF: 0.00312

Gnomad4 NFE AF: 0.00327

Gnomad4 OTH AF: 0.0468

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

Aug 13, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373626774; hg19: chr2-223065753;