Variant chrX-71290651-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4

The NM_007363.5(NONO):c.14A>T(p.Lys5Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000912 in 1,096,681 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

NONO
NM_007363.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.13

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 4 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate (size 0) in uniprot entity NONO_HUMAN

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=0.31989157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NONO	NM_007363.5 linkuse as main transcript	c.14A>T	p.Lys5Ile	missense_variant	3/12	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2 linkuse as main transcript	c.14A>T	p.Lys5Ile	missense_variant	4/13		NP_001138880.1
NONO	NM_001145409.2 linkuse as main transcript	c.14A>T	p.Lys5Ile	missense_variant	2/11		NP_001138881.1
NONO	NM_001145410.2 linkuse as main transcript	c.-113-1128A>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.14A>T	p.Lys5Ile	missense_variant	3/12	1	NM_007363.5	ENSP00000276079	P1	Q15233-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096681

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362183

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

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

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

.;.;D;D;D;D;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.32

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

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

M;M;M;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.13

Sift

Uncertain

0.0020

D;D;D;D;D;D;D

Sift4G

Uncertain

0.053

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

Polyphen

0.79

P;P;P;.;.;.;.

Vest4

0.52

MutPred

0.36

Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);Loss of ubiquitination at F5 (P = 0.0023);

MVP

0.78

MPC

2.6

ClinPred

0.89

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over