NM_181458.4:c.*107_*109delGGG

Variant names:

• chr2-222201298-ACCC-A
• rs3832105
• NM_181458.4:c.*107_*109delGGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181458.4(PAX3):​c.*107_*109delGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,450,444 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000034 (1 hom.)
• Consequence: PAX3 NM_181458.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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]

PAX3 Gene-Disease associations (from GenCC):

• craniofacial-deafness-hand syndrome

  Inheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Waardenburg syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Waardenburg syndrome type 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Waardenburg syndrome type 3

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX3	NM_181458.4	c.*107_*109delGGG		3_prime_UTR_variant	Exon 9 of 9	ENST00000392070.7	NP_852123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX3	ENST00000392070.7	c.*107_*109delGGG		3_prime_UTR_variant	Exon 9 of 9	1	NM_181458.4	ENSP00000375922.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1450444 Hom.: 1 AF XY: 0.00000554 AC XY: 4 AN XY: 721752

African (AFR) AF: 0.00 AC: 0 AN: 32944

American (AMR) AF: 0.00 AC: 0 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 35672

South Asian (SAS) AF: 0.0000585 AC: 5 AN: 85522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107716

Other (OTH) AF: 0.00 AC: 0 AN: 59824

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs3832105; hg19: chr2-223066017;