chrX-71290706-C-CCACCAGCAGCAG

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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]

NONO Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• syndromic X-linked intellectual disability 34

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007363.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NONO	NM_007363.5	MANE Select	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 3 of 12	NP_031389.3
	NONO	NM_001145408.2		c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 4 of 13	NP_001138880.1	A0A0S2Z4Z9
	NONO	NM_001145409.2		c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 2 of 11	NP_001138881.1	Q15233-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NONO	ENST00000276079.13	TSL:1 MANE Select	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 3 of 12	ENSP00000276079.8	Q15233-1
	NONO	ENST00000373856.8	TSL:1	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000362963.4	A0A7P0MRW0
	NONO	ENST00000373841.5	TSL:1	c.75_86dupGCAGCAGCACCA	p.Gln25_His28dup	disruptive_inframe_insertion	Exon 2 of 11	ENSP00000362947.1	Q15233-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-70510556;