NM_007363.5:c.84_95dupCCACCAGCAGCA

Variant names:

• chrX-71290712-G-GCAGCAGCACCAC
• rs1284257748
• NM_007363.5:c.84_95dupCCACCAGCAGCA

Variant summary

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

The NM_007363.5(NONO):​c.84_95dupCCACCAGCAGCA​(p.His28_Gln31dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,089,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: NONO NM_007363.5 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.56

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NONO	NM_007363.5	c.84_95dupCCACCAGCAGCA	p.His28_Gln31dup	disruptive_inframe_insertion	Exon 3 of 12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.84_95dupCCACCAGCAGCA	p.His28_Gln31dup	disruptive_inframe_insertion	Exon 4 of 13		NP_001138880.1
NONO	NM_001145409.2	c.84_95dupCCACCAGCAGCA	p.His28_Gln31dup	disruptive_inframe_insertion	Exon 2 of 11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1058_-113-1047dupCCACCAGCAGCA		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.84_95dupCCACCAGCAGCA	p.His28_Gln31dup	disruptive_inframe_insertion	Exon 3 of 12	1	NM_007363.5	ENSP00000276079.8

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000551 AC: 6 AN: 1089297 Hom.: 0 Cov.: 29 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000717

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 07, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Uncertain:1

Mar 02, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. ClinVar contains an entry for this variant (Variation ID: 985055). 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_95dup, results in the insertion of 4 amino acid(s) of the NONO protein (p.His28_Gln31dup), but otherwise preserves the integrity of the reading frame. -

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: rs1284257748; hg19: chrX-70510562;