chr1-18635222-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001135254.2(PAX7):c.433C>T(p.Arg145Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PAX7
NM_001135254.2 stop_gained
NM_001135254.2 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.18
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-18635222-C-T is Pathogenic according to our data. Variant chr1-18635222-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 689506.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-18635222-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAX7 | NM_001135254.2 | c.433C>T | p.Arg145Ter | stop_gained | 3/9 | ENST00000420770.7 | |
PAX7 | NM_002584.3 | c.433C>T | p.Arg145Ter | stop_gained | 3/8 | ||
PAX7 | NM_013945.3 | c.433C>T | p.Arg145Ter | stop_gained | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAX7 | ENST00000420770.7 | c.433C>T | p.Arg145Ter | stop_gained | 3/9 | 1 | NM_001135254.2 | P1 | |
PAX7 | ENST00000375375.7 | c.433C>T | p.Arg145Ter | stop_gained | 3/8 | 1 | |||
PAX7 | ENST00000400661.3 | c.433C>T | p.Arg145Ter | stop_gained | 3/8 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461418Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727030
GnomAD4 exome
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3
AN:
1461418
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Cov.:
31
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AC XY:
1
AN XY:
727030
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Myopathy, congenital, progressive, with scoliosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at