Genetic Variant NM_024053.5:c.32C>G (chr22-41947045-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024053.5(CENPM):c.32C>G(p.Pro11Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CENPM
NM_024053.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Publications

0 publications found

Variant links:

Genes affected

CENPM (HGNC:18352): (centromere protein M) The protein encoded by this gene is an inner protein of the kinetochore, the multi-protein complex that binds spindle microtubules to regulate chromosome segregation during cell division. It belongs to the constitutive centromere-associated network protein group, whose members interact with outer kinetochore proteins and help to maintain centromere identity at each cell division cycle. The protein is structurally related to GTPases but cannot bind guanosine triphosphate. A point mutation that affects interaction with another constitutive centromere-associated network protein, CENP-I, impairs kinetochore assembly and chromosome alignment, suggesting that it is required for kinetochore formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

CENPM links:

SMIM45 (HGNC:27930): (small integral membrane protein 45) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM45 links:

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ACMG classification

Classification was made for transcript

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, 0.928

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024053.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPM	NM_024053.5	MANE Select	c.32C>G	p.Pro11Arg	missense	Exon 1 of 6	NP_076958.1	Q9NSP4-1
CENPM	NM_001304371.2		c.32C>G	p.Pro11Arg	missense	Exon 1 of 4	NP_001291300.1	Q9NSP4-2
CENPM	NM_001002876.3		c.32C>G	p.Pro11Arg	missense	Exon 1 of 5	NP_001002876.1	Q9NSP4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPM	ENST00000215980.10	TSL:1 MANE Select	c.32C>G	p.Pro11Arg	missense	Exon 1 of 6	ENSP00000215980.5	Q9NSP4-1
CENPM	ENST00000921396.1		c.32C>G	p.Pro11Arg	missense	Exon 1 of 7	ENSP00000591455.1
CENPM	ENST00000921393.1		c.32C>G	p.Pro11Arg	missense	Exon 1 of 6	ENSP00000591452.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.93

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

2.9

PhyloP100

5.0

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.72

MutPred

0.73

Gain of MoRF binding (P = 0.0169)

MVP

0.36

MPC

1.1

ClinPred

1.0

GERP RS

4.6

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.89

gMVP

0.69

Mutation Taster

=61/39

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over