X-71290712-GCAGCAGCACCAC-G

Position:

• chrX-71290712-GCAGCAGCACCAC-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007363.5(NONO):​c.84_95del​(p.His28_Gln31del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: NONO NM_007363.5 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NONO	NM_007363.5	c.84_95del	p.His28_Gln31del	inframe_deletion	3/12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.84_95del	p.His28_Gln31del	inframe_deletion	4/13		NP_001138880.1
NONO	NM_001145409.2	c.84_95del	p.His28_Gln31del	inframe_deletion	2/11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1058_-113-1047del		intron_variant			NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13	c.84_95del	p.His28_Gln31del	inframe_deletion	3/12	1	NM_007363.5	ENSP00000276079	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000367 AC: 4 AN: 1089297 Hom.: 0 AF XY: 0.00000281 AC XY: 1 AN XY: 355537

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000239

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2022

This variant has not been reported in the literature in individuals affected with NONO-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.84_95del, results in the deletion of 4 amino acid(s) of the NONO protein (p.His28_Gln31del), but otherwise preserves the integrity of the reading frame. 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70510562;