5-55231638-C-G

Position:

• chr5-55231638-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021147.5(CCNO):​c.790G>C​(p.Gly264Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00124 in 1,599,092 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (7 hom.)
• Consequence: CCNO NM_021147.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.12

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009183466).
• BP6: Variant 5-55231638-C-G is Benign according to our data. Variant chr5-55231638-C-G is described in ClinVar as [Benign]. Clinvar id is 416793.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 = 0.00656 (1000/152358) while in subpopulation AFR AF= 0.0228 (950/41584). AF 95% confidence interval is 0.0216. There are 14 homozygotes in gnomad4. There are 441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNO	NM_021147.5	c.790G>C	p.Gly264Arg	missense_variant	3/3	ENST00000282572.5	NP_066970.3
CCNO	NR_125346.2	n.1251G>C		non_coding_transcript_exon_variant	3/3
CCNO	NR_125347.2	n.880G>C		non_coding_transcript_exon_variant	3/3
CCNO	NR_125348.1	n.854G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNO	ENST00000282572.5	c.790G>C	p.Gly264Arg	missense_variant	3/3	1	NM_021147.5	ENSP00000282572.4
CCNO	ENST00000501463.2	n.*770G>C		non_coding_transcript_exon_variant	3/3	1		ENSP00000422485.1
CCNO	ENST00000501463.2	n.*770G>C		3_prime_UTR_variant	3/3	1		ENSP00000422485.1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 994 AN: 152240 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00166 AC: 358 AN: 216294 Hom.: 3 AF XY: 0.00105 AC XY: 124 AN XY: 117956

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.000875

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000351

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000849

Gnomad OTH exome AF: 0.000737

GnomAD4 exome AF: 0.000675 AC: 977 AN: 1446734 Hom.: 7 Cov.: 31 AF XY: 0.000558 AC XY: 401 AN XY: 718758

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000472

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000389

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00656 AC: 1000 AN: 152358 Hom.: 14 Cov.: 33 AF XY: 0.00592 AC XY: 441 AN XY: 74518

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00190 Hom.: 0

Bravo AF: 0.00752

ESP6500AA AF: 0.0221 AC: 97

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00186 AC: 225

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.025
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.62		Gain of loop (P = 0.1069);
MVP		0.69
MPC		0.97
ClinPred		0.020	T
GERP RS		4.4
Varity_R		0.52
gMVP		0.58

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: rs138440180; hg19: chr5-54527466;