rs1367411

Variant names:

• chr2-222241123-C-A
• rs1367411
• NM_181458.4:c.587-8840G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-222241123-C-A
• chr2-222241123-C-G
• chr2-222241123-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181458.4(PAX3):​c.587-8840G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,452 control chromosomes in the GnomAD database, including 26,356 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 0.58 (26356 hom., cov: 32)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 2 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: G2P, Orphanet, 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Waardenburg syndrome type 3

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX3	NM_181458.4	MANE Select	c.587-8840G>T		intron	N/A	NP_852123.1	P23760-7
	PAX3	NM_181459.4		c.587-8840G>T		intron	N/A	NP_852124.1	P23760-8
	PAX3	NM_001127366.3		c.584-8840G>T		intron	N/A	NP_001120838.1	P23760-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX3	ENST00000392070.7	TSL:1 MANE Select	c.587-8840G>T		intron	N/A	ENSP00000375922.3	P23760-7
	PAX3	ENST00000409551.7	TSL:1	c.584-8840G>T		intron	N/A	ENSP00000386750.3	P23760-6
	PAX3	ENST00000336840.11	TSL:1	c.587-8840G>T		intron	N/A	ENSP00000338767.5	P23760-5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 87997 AN: 151334 Hom.: 26324 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.582 AC: 88086 AN: 151452 Hom.: 26356 Cov.: 32 AF XY: 0.588 AC XY: 43502 AN XY: 73968

African (AFR) AF: 0.684 AC: 28198 AN: 41250

American (AMR) AF: 0.683 AC: 10387 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4248 AN: 5130

South Asian (SAS) AF: 0.573 AC: 2756 AN: 4812

European-Finnish (FIN) AF: 0.585 AC: 6116 AN: 10456

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33001 AN: 67820

Other (OTH) AF: 0.576 AC: 1214 AN: 2106

Alfa AF: 0.448 Hom.: 2513

Bravo AF: 0.597

Asia WGS AF: 0.698 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.59
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs1367411; hg19: chr2-223105842;