X-71290703-TCACCACCAGCAGCAG-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_007363.5(NONO):c.81_95delGCACCACCAGCAGCA(p.His28_Gln32del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000512 in 1,093,127 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.000051 ( 0 hom. 14 hem. )
Consequence
NONO
NM_007363.5 disruptive_inframe_deletion
NM_007363.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.85
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 Likely_benign. Variant got -4 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 14 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NONO | NM_007363.5 | c.81_95delGCACCACCAGCAGCA | p.His28_Gln32del | disruptive_inframe_deletion | 3/12 | ENST00000276079.13 | NP_031389.3 | |
NONO | NM_001145408.2 | c.81_95delGCACCACCAGCAGCA | p.His28_Gln32del | disruptive_inframe_deletion | 4/13 | NP_001138880.1 | ||
NONO | NM_001145409.2 | c.81_95delGCACCACCAGCAGCA | p.His28_Gln32del | disruptive_inframe_deletion | 2/11 | NP_001138881.1 | ||
NONO | NM_001145410.2 | c.-113-1061_-113-1047delGCACCACCAGCAGCA | intron_variant | NP_001138882.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.0000116 AC: 2AN: 171854Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 58720
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GnomAD4 exome AF: 0.0000512 AC: 56AN: 1093127Hom.: 0 AF XY: 0.0000390 AC XY: 14AN XY: 358757
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GnomAD4 genome Cov.: 23
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | NONO: PM2, BP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 11, 2024 | This variant, c.81_95del, results in the deletion of 5 amino acid(s) of the NONO protein (p.His28_Gln32del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs756534222, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NONO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1319296). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Syndromic X-linked intellectual disability 34 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre | Apr 04, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at