chrX-71290703-TCACCACCAGCAGCAG-T

Position:

• 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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 3.85

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 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
NONO	NM_007363.5	c.81_95delGCACCACCAGCAGCA	p.His28_Gln32del	disruptive_inframe_deletion	3/12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.81_95delGCACCACCAGCAGCA	p.His28_Gln32del	disruptive_inframe_deletion	4/13		NP_001138880.1
NONO	NM_001145409.2	c.81_95delGCACCACCAGCAGCA	p.His28_Gln32del	disruptive_inframe_deletion	2/11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1061_-113-1047delGCACCACCAGCAGCA		intron_variant			NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13	c.81_95delGCACCACCAGCAGCA	p.His28_Gln32del	disruptive_inframe_deletion	3/12	1	NM_007363.5	ENSP00000276079.8

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

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

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	NONO: PM2, BP3 -

Syndromic X-linked intellectual disability 34 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Apr 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs756534222; hg19: chrX-70510553;