rs1555950011
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_007363.5(NONO):c.731dup(p.Asn244LysfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
NONO
NM_007363.5 frameshift
NM_007363.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.117
Genes affected
NONO (HGNC:7871): (non-POU domain containing octamer binding) This gene encodes an RNA-binding protein which plays various roles in the nucleus, including transcriptional regulation and RNA splicing. A rearrangement between this gene and the transcription factor E3 gene has been observed in papillary renal cell carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes exist on Chromosomes 2 and 16. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 X-71296639-T-TA is Pathogenic according to our data. Variant chrX-71296639-T-TA is described in ClinVar as [Pathogenic]. Clinvar id is 438778.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NONO | NM_007363.5 | c.731dup | p.Asn244LysfsTer21 | frameshift_variant | 6/12 | ENST00000276079.13 | |
NONO | NM_001145408.2 | c.731dup | p.Asn244LysfsTer21 | frameshift_variant | 7/13 | ||
NONO | NM_001145409.2 | c.731dup | p.Asn244LysfsTer21 | frameshift_variant | 5/11 | ||
NONO | NM_001145410.2 | c.464dup | p.Asn155LysfsTer21 | frameshift_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NONO | ENST00000276079.13 | c.731dup | p.Asn244LysfsTer21 | frameshift_variant | 6/12 | 1 | NM_007363.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Syndromic X-linked intellectual disability 34 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | - | This frameshifting variant in exon 6 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. Loss-of-function variation in NONO is a known mechanism of disease for X-linked syndromic intellectual developmental disorder-34 (MRXS34) (PMID: 26571461, 27329731, 27550220, 32397791). The NONO gene is highly constrained (Z-score= 3.59 and pLI = 0.99), which suggests it is intolerant to variation. The c.731dup (p.Asn244LysfsTer21) variant is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.731dup (p.Asn244LysfsTer21) variant is classified as Pathogenic. - |
Medulloblastoma Other:1
other, no assertion criteria provided | clinical testing | Donald Williams Parsons Laboratory, Baylor College of Medicine | May 01, 2016 | - 3: Mutations in other consensus cancer genes, not currently considered targetable |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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