rs780967882

Positions:

• chr5-55231479-T-C
• chr5-55231479-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021147.5(CCNO):​c.949A>G​(p.Met317Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCNO NM_021147.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07334164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNO	NM_021147.5	c.949A>G	p.Met317Val	missense_variant	3/3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1410A>G		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2	n.1039A>G		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1	n.1013A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.949A>G	p.Met317Val	missense_variant	3/3	1	NM_021147.5	ENSP00000282572	P1
CCNO	ENST00000501463.2	c.*929A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	1		ENSP00000422485

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.61
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.022
Sift	Benign	0.50	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.33		Loss of ubiquitination at K319 (P = 0.0603);
MVP		0.16
MPC		0.42
ClinPred		0.051	T
GERP RS		1.8
Varity_R		0.063
gMVP		0.20

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

Other links and lift over

dbSNP: rs780967882; hg19: chr5-54527307;