X-71290701-C-T

Position:

• chrX-71290701-C-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.64C>T​(p.His22Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NONO NM_007363.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

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=0.20194164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NONO	NM_007363.5	c.64C>T	p.His22Tyr	missense_variant	3/12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.64C>T	p.His22Tyr	missense_variant	4/13		NP_001138880.1
NONO	NM_001145409.2	c.64C>T	p.His22Tyr	missense_variant	2/11		NP_001138881.1
NONO	NM_001145410.2	c.-113-1078C>T		intron_variant			NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13	c.64C>T	p.His22Tyr	missense_variant	3/12	1	NM_007363.5	ENSP00000276079.8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 24, 2019

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T;T;T;T;.
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	.;.;D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L;L;L;.;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.86	N;N;N;N;N;D;N
REVEL	Benign	0.14
Sift	Benign	0.33	T;T;T;T;T;T;D
Sift4G	Benign	0.55	T;T;T;D;T;D;T
Polyphen		0.66	P;P;P;.;.;.;.
Vest4		0.38
MutPred		0.13		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP		0.63
MPC		1.5
ClinPred		0.73	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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-70510551;