chr2-222201151-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_181458.4(PAX3):c.*257G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,612,482 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 13 hom. )
Consequence
PAX3
NM_181458.4 3_prime_UTR
NM_181458.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.111
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 2-222201151-C-A is Benign according to our data. Variant chr2-222201151-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1684057.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00025 (38/152058) while in subpopulation EAS AF= 0.00348 (18/5170). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAX3 | NM_181458.4 | c.*257G>T | 3_prime_UTR_variant | 9/9 | ENST00000392070.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAX3 | ENST00000392070.7 | c.*257G>T | 3_prime_UTR_variant | 9/9 | 1 | NM_181458.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000244 AC: 37AN: 151940Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000435 AC: 109AN: 250408Hom.: 2 AF XY: 0.000517 AC XY: 70AN XY: 135354
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GnomAD4 exome AF: 0.000426 AC: 622AN: 1460424Hom.: 13 Cov.: 32 AF XY: 0.000501 AC XY: 364AN XY: 726582
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GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74322
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2021 | See Variant Classification Assertion Criteria. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at