rs797045150

Variant names:

• chr5-55231712-T-C
• rs797045150
• NM_021147.5:c.716A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021147.5(CCNO):​c.716A>G​(p.His239Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H239D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCNO NM_021147.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80
• Publications: 1 publications found

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]

CCNO Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 29

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNO	NM_021147.5	c.716A>G	p.His239Arg	missense_variant	Exon 3 of 3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1177A>G		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125347.2	n.806A>G		non_coding_transcript_exon_variant	Exon 3 of 3
CCNO	NR_125348.1	n.780A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.716A>G	p.His239Arg	missense_variant	Exon 3 of 3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2	n.*696A>G		non_coding_transcript_exon_variant	Exon 3 of 3	1		ENSP00000422485.1
CCNO	ENST00000501463.2	n.*696A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426236 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706238

African (AFR) AF: 0.00 AC: 0 AN: 32834

American (AMR) AF: 0.00 AC: 0 AN: 38572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 38024

South Asian (SAS) AF: 0.00 AC: 0 AN: 82140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094644

Other (OTH) AF: 0.00 AC: 0 AN: 59044

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.69
Sift	Benign	0.16	T
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.69		Loss of catalytic residue at H239 (P = 0.0797);
MVP		0.76
MPC		1.4
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.55
Mutation Taster		=26/74	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs797045150; hg19: chr5-54527540;