X-71290706-C-CCACCAGCAGCAG

Variant names:

• chrX-71290706-C-CCACCAGCAGCAG
• NM_007363.5:c.75_86dupGCAGCAGCACCA

Variant summary

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

The NM_007363.5(NONO):​c.75_86dupGCAGCAGCACCA​(p.Gln25_His28dup) variant causes a disruptive inframe insertion 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NONO NM_007363.5 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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 rank	MANE	Protein	UniProt
NONO	NM_007363.5	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 3 of 12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 4 of 13		NP_001138880.1
NONO	NM_001145409.2	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 2 of 11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1067_-113-1056dupGCAGCAGCACCA		intron_variant	Intron 1 of 9		NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 3 of 12	1	NM_007363.5	ENSP00000276079.8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is not present in population databases (gnomAD no frequency). This variant, c.75_86dup, results in the insertion of 4 amino acid(s) of the NONO protein (p.Gln25_His28dup), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with NONO-related conditions. 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-70510556;