NM_001387287.1:c.466G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387287.1(CENPL):​c.466G>A​(p.Val156Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CENPL
NM_001387287.1 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.353

Publications

0 publications found
Variant links:
Genes affected
CENPL (HGNC:17879): (centromere protein L) CENPL is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006) [PubMed 16622420].[supplied by OMIM, Mar 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19255596).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPLNM_001387287.1 linkc.466G>A p.Val156Met missense_variant Exon 5 of 6 ENST00000682279.1 NP_001374216.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPLENST00000682279.1 linkc.466G>A p.Val156Met missense_variant Exon 5 of 6 NM_001387287.1 ENSP00000507473.1 Q8N0S6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1453026
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
721390
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33160
American (AMR)
AF:
0.00
AC:
0
AN:
43830
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25848
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39504
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85346
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53328
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5706
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1106400
Other (OTH)
AF:
0.0000167
AC:
1
AN:
59904
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 05, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.604G>A (p.V202M) alteration is located in exon 6 (coding exon 4) of the CENPL gene. This alteration results from a G to A substitution at nucleotide position 604, causing the valine (V) at amino acid position 202 to be replaced by a methionine (M). 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
0.16
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
.;T;T
Eigen
Benign
0.17
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.76
T;.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.2
.;M;M
PhyloP100
0.35
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.078
Sift
Uncertain
0.0080
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.98
D;B;B
Vest4
0.29
MutPred
0.34
.;Loss of methylation at K155 (P = 0.0388);Loss of methylation at K155 (P = 0.0388);
MVP
0.57
MPC
0.46
ClinPred
0.85
D
GERP RS
4.0
Varity_R
0.077
gMVP
0.38
Mutation Taster
=85/15
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

Publications

Other links and lift over

dbSNP: rs1649939129; hg19: chr1-173772598; COSMIC: COSV61893020; API