rs115697956
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_021147.5(CCNO):c.1007C>T(p.Pro336Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000266 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
CCNO
NM_021147.5 missense
NM_021147.5 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 4.44
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 Benign. Variant got -14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.006074935).
BP6
Variant 5-55231421-G-A is Benign according to our data. Variant chr5-55231421-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 525497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00148 (226/152296) while in subpopulation AFR AF= 0.00517 (215/41550). AF 95% confidence interval is 0.00461. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCNO | NM_021147.5 | c.1007C>T | p.Pro336Leu | missense_variant | 3/3 | ENST00000282572.5 | NP_066970.3 | |
CCNO | NR_125346.2 | n.1468C>T | non_coding_transcript_exon_variant | 3/3 | ||||
CCNO | NR_125347.2 | n.1097C>T | non_coding_transcript_exon_variant | 3/3 | ||||
CCNO | NR_125348.1 | n.1071C>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCNO | ENST00000282572.5 | c.1007C>T | p.Pro336Leu | missense_variant | 3/3 | 1 | NM_021147.5 | ENSP00000282572.4 | ||
CCNO | ENST00000501463.2 | n.*987C>T | non_coding_transcript_exon_variant | 3/3 | 1 | ENSP00000422485.1 | ||||
CCNO | ENST00000501463.2 | n.*987C>T | 3_prime_UTR_variant | 3/3 | 1 | ENSP00000422485.1 |
Frequencies
GnomAD3 genomes AF: 0.00149 AC: 226AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000402 AC: 101AN: 251358Hom.: 0 AF XY: 0.000309 AC XY: 42AN XY: 135894
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GnomAD4 exome AF: 0.000140 AC: 204AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 727220
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GnomAD4 genome AF: 0.00148 AC: 226AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at