chrX-71290703-TCACCACCAGCAGCAG-T

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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 3.85
Variant links:
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]

Genome browser will be placed here

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
NONONM_007363.5 linkc.81_95delGCACCACCAGCAGCA p.His28_Gln32del disruptive_inframe_deletion 3/12 ENST00000276079.13 NP_031389.3 Q15233-1A0A0S2Z4Z9
NONONM_001145408.2 linkc.81_95delGCACCACCAGCAGCA p.His28_Gln32del disruptive_inframe_deletion 4/13 NP_001138880.1 Q15233-1A0A0S2Z4Z9
NONONM_001145409.2 linkc.81_95delGCACCACCAGCAGCA p.His28_Gln32del disruptive_inframe_deletion 2/11 NP_001138881.1 Q15233-1A0A0S2Z4Z9
NONONM_001145410.2 linkc.-113-1061_-113-1047delGCACCACCAGCAGCA intron_variant NP_001138882.1 Q15233-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NONOENST00000276079.13 linkc.81_95delGCACCACCAGCAGCA p.His28_Gln32del disruptive_inframe_deletion 3/121 NM_007363.5 ENSP00000276079.8 Q15233-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000116
AC:
2
AN:
171854
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
58720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000512
AC:
56
AN:
1093127
Hom.:
0
AF XY:
0.0000390
AC XY:
14
AN XY:
358757
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.0000375
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000524
Gnomad4 OTH exome
AF:
0.000131
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.0000189

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023NONO: PM2, BP3 -
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 11, 2024This 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 submitterclinical testingInstitute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU DresdenNov 03, 2021- -
Syndromic X-linked intellectual disability 34 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research CentreApr 04, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756534222; hg19: chrX-70510553; API