1-18703052-A-T

Variant names:

• chr1-18703052-A-T
• rs1416464
• NM_001135254.2:c.953-42A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135254.2(PAX7):​c.953-42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 7 publications found

Genes affected

PAX7 (HGNC:8621): (paired box 7) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The specific function of the paired box 7 gene is unknown but speculated to involve tumor suppression since fusion of this gene with a forkhead domain family member has been associated with alveolar rhabdomyosarcoma. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

PAX7 Gene-Disease associations (from GenCC):

• myopathy, congenital, progressive, with scoliosis

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• congenital myopathy with myasthenic-like onset

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX7	NM_001135254.2	MANE Select	c.953-42A>T		intron	N/A	NP_001128726.1
	PAX7	NM_002584.3		c.953-42A>T		intron	N/A	NP_002575.1
	PAX7	NM_013945.3		c.947-42A>T		intron	N/A	NP_039236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX7	ENST00000420770.7	TSL:1 MANE Select	c.953-42A>T		intron	N/A	ENSP00000403389.2
	PAX7	ENST00000375375.7	TSL:1	c.953-42A>T		intron	N/A	ENSP00000364524.3
	PAX7	ENST00000400661.3	TSL:1	c.947-42A>T		intron	N/A	ENSP00000383502.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1419744 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 704246

African (AFR) AF: 0.00 AC: 0 AN: 32558

American (AMR) AF: 0.00 AC: 0 AN: 43864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 39134

South Asian (SAS) AF: 0.00 AC: 0 AN: 85246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4822

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077412

Other (OTH) AF: 0.00 AC: 0 AN: 58552

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.42

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: rs1416464; hg19: chr1-19029546;