5-55231533-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021147.5(CCNO):​c.895C>T​(p.Arg299Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,564 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 4 hom. )

Consequence

CCNO
NM_021147.5 missense

Scores

2
17

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.011220634).
BP6
Variant 5-55231533-G-A is Benign according to our data. Variant chr5-55231533-G-A is described in ClinVar as [Benign]. Clinvar id is 2695498.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCNONM_021147.5 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant 3/3 ENST00000282572.5
CCNONR_125346.2 linkuse as main transcriptn.1356C>T non_coding_transcript_exon_variant 3/3
CCNONR_125347.2 linkuse as main transcriptn.985C>T non_coding_transcript_exon_variant 3/3
CCNONR_125348.1 linkuse as main transcriptn.959C>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCNOENST00000282572.5 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant 3/31 NM_021147.5 P1P22674-1
CCNOENST00000501463.2 linkuse as main transcriptc.*875C>T 3_prime_UTR_variant, NMD_transcript_variant 3/31 P22674-2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152206
Hom.:
1
Cov.:
33
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:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000260
AC:
65
AN:
250324
Hom.:
3
AF XY:
0.000347
AC XY:
47
AN XY:
135638
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:
0.00209
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000138
AC:
202
AN:
1461240
Hom.:
4
Cov.:
31
AF XY:
0.000188
AC XY:
137
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00224
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152324
Hom.:
1
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74482
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:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.000297
AC:
36
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 02, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.070
T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.58
N
REVEL
Benign
0.11
Sift
Benign
0.092
T
Sift4G
Uncertain
0.024
D
Polyphen
0.99
D
Vest4
0.20
MutPred
0.49
Loss of disorder (P = 0.0317);
MVP
0.50
MPC
0.43
ClinPred
0.13
T
GERP RS
-1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.074
gMVP
0.36

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.

Other links and lift over

dbSNP: rs538637609; hg19: chr5-54527361; API