2-24815518-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001322101.2(CENPO):c.356G>T(p.Ser119Ile) 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. 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. S119R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPO NM_001322101.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30895823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPO	NM_001322101.2	c.356G>T	p.Ser119Ile	missense_variant	5/8	ENST00000380834.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPO	ENST00000380834.7	c.356G>T	p.Ser119Ile	missense_variant	5/8	5	NM_001322101.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.356G>T (p.S119I) alteration is located in exon 5 (coding exon 4) of the CENPO gene. This alteration results from a G to T substitution at nucleotide position 356, causing the serine (S) at amino acid position 119 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L;.;L
MutationTaster	Benign	0.61	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.025	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.42
MutPred		0.43		Loss of catalytic residue at S119 (P = 0.0099);.;Loss of catalytic residue at S119 (P = 0.0099);
MVP		0.48
MPC		0.59
ClinPred		0.92	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-25038387;