X-71290755-C-T

Variant names:

• chrX-71290755-C-T
• NM_007363.5:c.118C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007363.5(NONO):​c.118C>T​(p.Pro40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: NONO NM_007363.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.02

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11193758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NONO	NM_007363.5	c.118C>T	p.Pro40Ser	missense_variant	Exon 3 of 12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.118C>T	p.Pro40Ser	missense_variant	Exon 4 of 13		NP_001138880.1
NONO	NM_001145409.2	c.118C>T	p.Pro40Ser	missense_variant	Exon 2 of 11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1024C>T		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.118C>T	p.Pro40Ser	missense_variant	Exon 3 of 12	1	NM_007363.5	ENSP00000276079.8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.29e-7 AC: 1 AN: 1076168 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 347442

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: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

NONO-related disorder Uncertain:1

May 25, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The NONO c.118C>T variant is predicted to result in the amino acid substitution p.Pro40Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T;T;T;T;.
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.76	.;.;T;T;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.48	N;N;N;N;N;D;N
REVEL	Benign	0.030
Sift	Benign	0.13	T;T;T;T;T;T;T
Sift4G	Benign	0.43	T;T;T;T;T;D;T
Polyphen		0.0050	B;B;B;.;.;.;.
Vest4		0.24
MutPred		0.19		Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);Gain of phosphorylation at P40 (P = 0.0189);
MVP		0.61
MPC		1.4
ClinPred		0.16	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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-70510605;