rs1555949579

Variant names:

• chrX-71294429-G-C
• rs1555949579
• NM_007363.5:c.551G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007363.5(NONO):​c.551G>C​(p.Arg184Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.83
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NONO	NM_007363.5	c.551G>C	p.Arg184Pro	missense_variant	Exon 5 of 12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2	c.551G>C	p.Arg184Pro	missense_variant	Exon 6 of 13		NP_001138880.1
NONO	NM_001145409.2	c.551G>C	p.Arg184Pro	missense_variant	Exon 4 of 11		NP_001138881.1
NONO	NM_001145410.2	c.284G>C	p.Arg95Pro	missense_variant	Exon 3 of 10		NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13	c.551G>C	p.Arg184Pro	missense_variant	Exon 5 of 12	1	NM_007363.5	ENSP00000276079.8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 10, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;T;T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L;L;L;.
PhyloP100		9.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.6	D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;T
Polyphen		1.0	.;D;D;D;.
Vest4		0.62
MutPred		0.49		.;Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);
MVP		0.89
MPC		3.0
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.99
gMVP		0.98
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1555949579; hg19: chrX-70514279;