NM_007363.5:c.84_92delCCACCAGCA

Variant names:

• chrX-71290715-GCAGCACCAC-G
• rs767983134
• NM_007363.5:c.84_92delCCACCAGCA

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_007363.5(NONO):​c.84_92delCCACCAGCA​(p.His28_Gln30del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000141 in 1,201,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000014 (0 hom. 7 hem.)
• Consequence: NONO NM_007363.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.33
• 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007363.5
• BP6: Variant X-71290715-GCAGCACCAC-G is Benign according to our data. Variant chrX-71290715-GCAGCACCAC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3698305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 7 XL gene

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.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 3 of 12	NP_031389.3
	NONO	NM_001145408.2		c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 4 of 13	NP_001138880.1	A0A0S2Z4Z9
	NONO	NM_001145409.2		c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	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.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 3 of 12	ENSP00000276079.8	Q15233-1
	NONO	ENST00000373856.8	TSL:1	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 3 of 13	ENSP00000362963.4	A0A7P0MRW0
	NONO	ENST00000373841.5	TSL:1	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000362947.1	Q15233-1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112151 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 4 AN: 165982 AF XY: 0.0000368

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000422

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 15 AN: 1089503 Hom.: 0 AF XY: 0.0000197 AC XY: 7 AN XY: 355811

African (AFR) AF: 0.00 AC: 0 AN: 26202

American (AMR) AF: 0.00 AC: 0 AN: 34534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19156

East Asian (EAS) AF: 0.0000666 AC: 2 AN: 30052

South Asian (SAS) AF: 0.0000377 AC: 2 AN: 53081

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4109

European-Non Finnish (NFE) AF: 0.0000120 AC: 10 AN: 836601

Other (OTH) AF: 0.0000219 AC: 1 AN: 45730

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112206 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34368

African (AFR) AF: 0.00 AC: 0 AN: 30900

American (AMR) AF: 0.00 AC: 0 AN: 10541

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3596

South Asian (SAS) AF: 0.00 AC: 0 AN: 2718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53259

Other (OTH) AF: 0.00 AC: 0 AN: 1535

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

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		4.3
Mutation Taster		=186/14	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs767983134; hg19: chrX-70510565;