Variant 2-222201151-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000392070.7(PAX3):c.*257G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,611,526 control chromosomes in the GnomAD database, including 31,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2231 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29638 hom. )

Consequence

PAX3
ENST00000392070.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.111

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-222201151-C-G is Benign according to our data. Variant chr2-222201151-C-G is described in ClinVar as [Benign]. Clinvar id is 1244902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-222201151-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX3	NM_181458.4 linkuse as main transcript	c.*257G>C		3_prime_UTR_variant	9/9	ENST00000392070.7	NP_852123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX3	ENST00000392070.7 linkuse as main transcript	c.*257G>C		3_prime_UTR_variant	9/9	1	NM_181458.4	ENSP00000375922	A1	P23760-7

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22822

AN:

151908

Hom.:

2230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.191

AC:

47808

AN:

250408

Hom.:

4975

AF XY:

0.198

AC XY:

26746

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.285

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.198

AC:

288564

AN:

1459500

Hom.:

29638

Cov.:

AF XY:

0.200

AC XY:

145400

AN XY:

726182

show subpopulations

Gnomad4 AFR exome

AF:

0.0319

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.273

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.150

AC:

22818

AN:

152026

Hom.:

2231

Cov.:

AF XY:

0.150

AC XY:

11181

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.129

Hom.:

343

Bravo

AF:

0.143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.3

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over