1-173803501-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387287.1(CENPL):ā€‹c.425T>Cā€‹(p.Val142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CENPL
NM_001387287.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.024333417).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CENPLNM_001387287.1 linkuse as main transcriptc.425T>C p.Val142Ala missense_variant 5/6 ENST00000682279.1 NP_001374216.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CENPLENST00000682279.1 linkuse as main transcriptc.425T>C p.Val142Ala missense_variant 5/6 NM_001387287.1 ENSP00000507473 P1Q8N0S6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1408112
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
693936
show subpopulations
Gnomad4 AFR exome
AF:
0.0000319
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:
0.00
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 19, 2024The c.563T>C (p.V188A) alteration is located in exon 6 (coding exon 4) of the CENPL gene. This alteration results from a T to C substitution at nucleotide position 563, causing the valine (V) at amino acid position 188 to be replaced by an alanine (A). 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
0.11
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.0050
.;T;T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.13
T;.;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.024
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
.;N;N
MutationTaster
Benign
0.97
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.056
Sift
Benign
0.34
T;T;T
Sift4G
Benign
0.23
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.059
MutPred
0.27
.;Loss of stability (P = 0.0351);Loss of stability (P = 0.0351);
MVP
0.11
MPC
0.14
ClinPred
0.33
T
GERP RS
2.5
Varity_R
0.043
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1649945397; hg19: chr1-173772639; API