Variant chrX-71290802-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007363.5(NONO):c.154+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,127,808 control chromosomes in the GnomAD database, including 22 homozygotes. There are 569 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 9 hom., 287 hem., cov: 24)

Exomes 𝑓: 0.0011 ( 13 hom. 282 hem. )

Consequence

NONO
NM_007363.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.407

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-71290802-G-C is Benign according to our data. Variant chrX-71290802-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1596235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00991 (1114/112384) while in subpopulation AFR AF= 0.0333 (1030/30962). AF 95% confidence interval is 0.0316. There are 9 homozygotes in gnomad4. There are 287 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NONO	NM_007363.5 linkuse as main transcript	c.154+11G>C	intron_variant	ENST00000276079.13	NP_031389.3
NONO	NM_001145408.2 linkuse as main transcript	c.154+11G>C	intron_variant		NP_001138880.1
NONO	NM_001145409.2 linkuse as main transcript	c.154+11G>C	intron_variant		NP_001138881.1
NONO	NM_001145410.2 linkuse as main transcript	c.-113-977G>C	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.154+11G>C		intron_variant		1	NM_007363.5	ENSP00000276079	P1	Q15233-1

Frequencies

GnomAD3 genomes

AF:

0.00993

AC:

1116

AN:

112332

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

287

AN XY:

34502

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00927

GnomAD3 exomes

AF:

0.00367

AC:

313

AN:

85390

Hom.:

AF XY:

0.00269

AC XY:

AN XY:

16000

show subpopulations

Gnomad AFR exome

AF:

0.0363

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000294

Gnomad OTH exome

AF:

0.000418

GnomAD4 exome

AF:

0.00107

AC:

1084

AN:

1015424

Hom.:

Cov.:

AF XY:

0.000893

AC XY:

282

AN XY:

315894

show subpopulations

Gnomad4 AFR exome

AF:

0.0373

Gnomad4 AMR exome

AF:

0.00299

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000237

Gnomad4 OTH exome

AF:

0.00276

GnomAD4 genome

AF:

0.00991

AC:

1114

AN:

112384

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

287

AN XY:

34564

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.00624

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00916

Alfa

AF:

0.00541

Hom.:

Bravo

AF:

0.0120

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Syndromic X-linked intellectual disability 34

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.3

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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