rs139606873

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_021147.5(CCNO):c.134C>A(p.Pro45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,610,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P45A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

CCNO
NM_021147.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0062422752).

BP6

Variant 5-55233390-G-T is Benign according to our data. Variant chr5-55233390-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 416791.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNO	NM_021147.5 link	c.134C>A	p.Pro45His	missense_variant	Exon 1 of 3	ENST00000282572.5	NP_066970.3	P22674-1
CCNO	NR_125346.2 link	n.219C>A		non_coding_transcript_exon_variant	Exon 1 of 3
CCNO	NR_125347.2 link	n.219C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5 link	c.134C>A	p.Pro45His	missense_variant	Exon 1 of 3	1	NM_021147.5	ENSP00000282572.4		P22674-1
CCNO	ENST00000501463.2 link	n.134C>A		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000422485.1		P22674-2

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00144

AC:

344

AN:

238122

AF XY:

0.00143

show subpopulations

Gnomad AFR exome

AF:

0.0000678

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000296

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.00133

AC:

1933

AN:

1458366

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

932

AN XY:

725390

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

AC:

AN:

33432

Gnomad4 AMR exome

AF:

0.00245

AC:

109

AN:

44556

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26060

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39640

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85950

Gnomad4 FIN exome

AF:

0.000601

AC:

AN:

51606

Gnomad4 NFE exome

AF:

0.00155

AC:

1718

AN:

1111160

Gnomad4 Remaining exome

AF:

0.00106

AC:

AN:

60210

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152298

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000265

AC:

0.000264576

AN:

0.000264576

Gnomad4 AMR

AF:

0.00261

AC:

0.00261267

AN:

0.00261267

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.000659

AC:

0.000658762

AN:

0.000658762

Gnomad4 NFE

AF:

0.00232

AC:

0.00232312

AN:

0.00232312

Gnomad4 OTH

AF:

0.00284

AC:

0.00283554

AN:

0.00283554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00151

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00199

AC:

ExAC

AF:

0.00162

AC:

196

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 29

Benign:1

Mar 20, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BS1, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.56

M_CAP

Benign

0.018

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

REVEL

Benign

0.036

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.018

Polyphen

0.41

Vest4

0.23

MVP

0.63

MPC

0.89

ClinPred

0.032

GERP RS

4.3

Varity_R

0.12

gMVP

0.34

Mutation Taster

=96/4

polymorphism

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over