Variant 5-55231640-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021147.5(CCNO):c.788G>A(p.Arg263Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,595,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

CCNO
NM_021147.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.324

Variant links:

Genes affected

CCNO (HGNC:18576): (cyclin O) This gene encodes a member of the cyclin protein family, and the encoded protein is involved in regulation of the cell cycle. Disruption of this gene is associated with primary ciliary dyskinesia-19. Alternative splicing results in multiple transcript variants. This gene, which has a previous symbol of UNG2, was erroneously identified as a uracil DNA glycosylase in PubMed ID: 2001396. A later publication, PubMed ID: 8419333, identified this gene's product as a cyclin protein family member. The UNG2 symbol is also used as a specific protein isoform name for the UNG gene (GeneID 7374), so confusion exists in the scientific literature and in some databases for these two genes. [provided by RefSeq, Jul 2014]

CCNO links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08804849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNO	NM_021147.5 link	c.788G>A	p.Arg263Gln	missense_variant	3/3	ENST00000282572.5	NP_066970.3	P22674-1
CCNO	NR_125346.2 link	n.1249G>A		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2 link	n.878G>A		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1 link	n.852G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCNO	ENST00000282572.5 link	c.788G>A	p.Arg263Gln	missense_variant	3/3	1	NM_021147.5	ENSP00000282572.4	P22674-1
CCNO	ENST00000501463.2 link	n.*768G>A		non_coding_transcript_exon_variant	3/3	1		ENSP00000422485.1	P22674-2
CCNO	ENST00000501463.2 link	n.*768G>A		3_prime_UTR_variant	3/3	1		ENSP00000422485.1	P22674-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000970

AC:

AN:

1443712

Hom.:

Cov.:

AF XY:

0.00000976

AC XY:

AN XY:

716996

show subpopulations

Gnomad4 AFR exome

AF:

0.0000906

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000997

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.73

M_CAP

Benign

0.0075

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.0060

Sift

Benign

0.18

Sift4G

Benign

0.29

Polyphen

0.11

Vest4

0.084

MutPred

0.45

Gain of loop (P = 0.1069);

MVP

0.26

MPC

0.49

ClinPred

0.16

GERP RS

1.3

Varity_R

0.12

gMVP

0.23

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over