chrX-71290763-T-C

Variant names:

• chrX-71290763-T-C
• rs996588311
• NM_007363.5:c.126T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_007363.5(NONO):​c.126T>C​(p.Pro42Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: NONO NM_007363.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.301
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-71290763-T-C is Benign according to our data. Variant chrX-71290763-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2028243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.301 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NONO	NM_007363.5	MANE Select	c.126T>C	p.Pro42Pro	synonymous	Exon 3 of 12	NP_031389.3
	NONO	NM_001145408.2		c.126T>C	p.Pro42Pro	synonymous	Exon 4 of 13	NP_001138880.1	A0A0S2Z4Z9
	NONO	NM_001145409.2		c.126T>C	p.Pro42Pro	synonymous	Exon 2 of 11	NP_001138881.1	Q15233-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NONO	ENST00000276079.13	TSL:1 MANE Select	c.126T>C	p.Pro42Pro	synonymous	Exon 3 of 12	ENSP00000276079.8	Q15233-1
	NONO	ENST00000373856.8	TSL:1	c.126T>C	p.Pro42Pro	synonymous	Exon 3 of 13	ENSP00000362963.4	A0A7P0MRW0
	NONO	ENST00000373841.5	TSL:1	c.126T>C	p.Pro42Pro	synonymous	Exon 2 of 11	ENSP00000362947.1	Q15233-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs996588311; hg19: chrX-70510613;