5-55232365-T-G

Variant names:

• chr5-55232365-T-G
• NM_021147.5:c.563A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021147.5(CCNO):​c.563A>C​(p.Lys188Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCNO NM_021147.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNO	NM_021147.5	c.563A>C	p.Lys188Thr	missense_variant	Exon 2 of 3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1024A>C		non_coding_transcript_exon_variant	Exon 2 of 3
CCNO	NR_125347.2	n.653A>C		non_coding_transcript_exon_variant	Exon 2 of 3
CCNO	NR_125348.1	n.627A>C		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.563A>C	p.Lys188Thr	missense_variant	Exon 2 of 3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2	n.*543A>C		non_coding_transcript_exon_variant	Exon 2 of 3	1		ENSP00000422485.1
CCNO	ENST00000501463.2	n.*543A>C		3_prime_UTR_variant	Exon 2 of 3	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461324 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.088	D
MutationAssessor	Pathogenic	4.3	H
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.78		Loss of methylation at K188 (P = 0.0043);
MVP		0.84
MPC		1.4
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.71
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-54528193;