chrX-71290741-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007363.5(NONO):c.104A>C(p.Gln35Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,075,324 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q35H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000037 ( 0 hom. 0 hem. )

Consequence

NONO
NM_007363.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P

NONO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13404292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NONO	NM_007363.5	MANE Select	c.104A>C	p.Gln35Pro	missense	Exon 3 of 12	NP_031389.3
NONO	NM_001145408.2		c.104A>C	p.Gln35Pro	missense	Exon 4 of 13	NP_001138880.1	A0A0S2Z4Z9
NONO	NM_001145409.2		c.104A>C	p.Gln35Pro	missense	Exon 2 of 11	NP_001138881.1	Q15233-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NONO	ENST00000276079.13	TSL:1 MANE Select	c.104A>C	p.Gln35Pro	missense	Exon 3 of 12	ENSP00000276079.8	Q15233-1
NONO	ENST00000373856.8	TSL:1	c.104A>C	p.Gln35Pro	missense	Exon 3 of 13	ENSP00000362963.4	A0A7P0MRW0
NONO	ENST00000373841.5	TSL:1	c.104A>C	p.Gln35Pro	missense	Exon 2 of 11	ENSP00000362947.1	Q15233-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

142959

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000372

AC:

AN:

1075324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

349086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26062

American (AMR)

AF:

0.00

AC:

AN:

33338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18684

East Asian (EAS)

AF:

0.00

AC:

AN:

29747

South Asian (SAS)

AF:

0.00

AC:

AN:

52320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

827203

Other (OTH)

AF:

0.0000222

AC:

AN:

45034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000179

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.14

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.65

M_CAP

Benign

0.026

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.9

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.27

REVEL

Benign

0.080

Sift

Benign

0.22

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.37

MutPred

0.34

Gain of glycosylation at Q35 (P = 0.0014)

MVP

0.68

MPC

2.1

ClinPred

0.24

GERP RS

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.46

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over