chr5-55231388-G-C

Variant summary

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

The NM_021147.5(CCNO):​c.1040C>G​(p.Pro347Arg) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P347L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CCNO
NM_021147.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.163
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]

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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=0.07572791).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCNONM_021147.5 linkuse as main transcriptc.1040C>G p.Pro347Arg missense_variant 3/3 ENST00000282572.5
CCNONR_125346.2 linkuse as main transcriptn.1501C>G non_coding_transcript_exon_variant 3/3
CCNONR_125347.2 linkuse as main transcriptn.1130C>G non_coding_transcript_exon_variant 3/3
CCNONR_125348.1 linkuse as main transcriptn.1104C>G 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.1040C>G p.Pro347Arg missense_variant 3/31 NM_021147.5 P1P22674-1
CCNOENST00000501463.2 linkuse as main transcriptc.*1020C>G 3_prime_UTR_variant, NMD_transcript_variant 3/31 P22674-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 03, 2022The c.1040C>G (p.P347R) alteration is located in exon 3 (coding exon 3) of the CCNO gene. This alteration results from a C to G substitution at nucleotide position 1040, causing the proline (P) at amino acid position 347 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
13
DANN
Benign
0.76
DEOGEN2
Benign
0.052
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.011
Sift
Benign
0.15
T
Sift4G
Benign
0.64
T
Polyphen
0.099
B
Vest4
0.20
MutPred
0.32
Loss of glycosylation at P347 (P = 0.0012);
MVP
0.25
MPC
0.61
ClinPred
0.069
T
GERP RS
-0.33
Varity_R
0.053
gMVP
0.28

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: rs547968661; hg19: chr5-54527216; API