Variant X-71290744-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_007363.5(NONO):c.107C>T(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,071,986 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

NONO
NM_007363.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NONO. . Gene score misZ 3.5885 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked syndromic intellectual disability, autism, susceptibility to, 15, syndromic X-linked intellectual disability 34.

BP4

Computational evidence support a benign effect (MetaRNN=0.088362515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NONO	NM_007363.5 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	3/12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	4/13		NP_001138880.1
NONO	NM_001145409.2 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	2/11		NP_001138881.1
NONO	NM_001145410.2 linkuse as main transcript	c.-113-1035C>T		intron_variant			NP_001138882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	3/12	1	NM_007363.5	ENSP00000276079	P1	Q15233-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000722

AC:

AN:

138417

Hom.:

AF XY:

0.0000249

AC XY:

AN XY:

40181

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000851

Gnomad SAS 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:

0.00000373

AC:

AN:

1071986

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

346822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000337

Gnomad4 SAS exome

AF:

0.0000386

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000182

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability 34

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jan 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.18

T;T;T;T;T;T;.

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.70

.;.;T;T;T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.088

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L;.;.;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.82

N;N;N;N;N;D;N

REVEL

Benign

0.058

Sift

Benign

0.093

T;T;T;T;T;D;T

Sift4G

Benign

0.067

T;T;T;T;T;T;T

Polyphen

0.14

B;B;B;.;.;.;.

Vest4

0.35

MutPred

0.23

Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);Loss of glycosylation at P36 (P = 0.0025);

MVP

0.48

MPC

1.3

ClinPred

0.089

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over