rs553551503

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024053.5(CENPM):​c.364C>T​(p.His122Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CENPM
NM_024053.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1469624).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPMNM_024053.5 linkc.364C>T p.His122Tyr missense_variant Exon 5 of 6 ENST00000215980.10 NP_076958.1 Q9NSP4-1A0A024R1Q3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPMENST00000215980.10 linkc.364C>T p.His122Tyr missense_variant Exon 5 of 6 1 NM_024053.5 ENSP00000215980.5 Q9NSP4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461572
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727084
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.065
T;.
Eigen
Benign
-0.029
Eigen_PC
Benign
-0.038
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.9
M;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.023
Sift
Benign
0.27
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.095
B;.
Vest4
0.30
MutPred
0.26
Loss of methylation at K119 (P = 0.0685);.;
MVP
0.26
MPC
0.44
ClinPred
0.071
T
GERP RS
1.9
Varity_R
0.13
gMVP
0.46

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: chr22-42339652; API