NM_001322101.2:c.169C>T

Variant names:

• chr2-24799797-C-T
• rs748592316
• NM_001322101.2:c.169C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001322101.2(CENPO):​c.169C>T​(p.Arg57Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R57H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: CENPO NM_001322101.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.546
• Publications: 1 publications found

Genes affected

CENPO (HGNC:28152): (centromere protein O) This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046053767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322101.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPO	NM_001322101.2	MANE Select	c.169C>T	p.Arg57Cys	missense	Exon 3 of 8	NP_001309030.1	Q9BU64-1
	CENPO	NM_024322.4		c.169C>T	p.Arg57Cys	missense	Exon 3 of 8	NP_077298.1	Q9BU64-1
	CENPO	NM_001199803.3		c.151C>T	p.Arg51Cys	missense	Exon 2 of 7	NP_001186732.1	Q9BU64-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPO	ENST00000380834.7	TSL:5 MANE Select	c.169C>T	p.Arg57Cys	missense	Exon 3 of 8	ENSP00000370214.2	Q9BU64-1
	CENPO	ENST00000260662.2	TSL:1	c.169C>T	p.Arg57Cys	missense	Exon 3 of 8	ENSP00000260662.1	Q9BU64-1
	CENPO	ENST00000868050.1		c.169C>T	p.Arg57Cys	missense	Exon 3 of 8	ENSP00000538109.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251460 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461542 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20 AN XY: 727068

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.1
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		-0.55
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.025
Sift	Benign	0.13	T
Sift4G	Benign	0.084	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.33		Loss of disorder (P = 0.0366)
MVP		0.25
MPC		0.18
ClinPred		0.040	T
GERP RS		-1.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.082
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748592316; hg19: chr2-25022666; COSMIC: COSV53229353; COSMIC: COSV53229353;