Genetic Variant NONO:p.His28_Gln30del (chrX-71290715-GCAGCACCAC-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_007363.5(NONO):c.84_92delCCACCAGCA(p.His28_Gln30del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000141 in 1,201,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000014 ( 0 hom. 7 hem. )

Consequence

NONO
NM_007363.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.33

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-71290715-GCAGCACCAC-G is Benign according to our data. Variant chrX-71290715-GCAGCACCAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3698305.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NONO	NM_007363.5 link	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 3 of 12	ENST00000276079.13	NP_031389.3	Q15233-1A0A0S2Z4Z9
NONO	NM_001145408.2 link	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 4 of 13		NP_001138880.1	Q15233-1A0A0S2Z4Z9
NONO	NM_001145409.2 link	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 2 of 11		NP_001138881.1	Q15233-1A0A0S2Z4Z9
NONO	NM_001145410.2 link	c.-113-1058_-113-1050delCCACCAGCA		intron_variant	Intron 1 of 9		NP_001138882.1	Q15233-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NONO	ENST00000276079.13 link	c.84_92delCCACCAGCA	p.His28_Gln30del	disruptive_inframe_deletion	Exon 3 of 12	1	NM_007363.5	ENSP00000276079.8		Q15233-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112151

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34303

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

165982

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

54408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000582

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000422

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1089503

Hom.:

AF XY:

0.0000197

AC XY:

AN XY:

355811

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000666

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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