Variant chr1-173803163-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001387287.1(CENPL):c.763G>A(p.Ala255Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CENPL
NM_001387287.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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]

CENPL links:

CENPL (HGNC:):

CENPL links:

Genome browser will be placed here

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=0.06981251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPL	NM_001387287.1 linkuse as main transcript	c.763G>A	p.Ala255Thr	missense_variant	5/6	ENST00000682279.1	NP_001374216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPL	ENST00000682279.1 linkuse as main transcript	c.763G>A	p.Ala255Thr	missense_variant	5/6		NM_001387287.1	ENSP00000507473.1		Q8N0S6-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251278

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.901G>A (p.A301T) 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 901, causing the alanine (A) at amino acid position 301 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

.;T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.86

D;.;D

M_CAP

Benign

0.0089

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

1.0

D;P;P

Vest4

0.22

MutPred

0.28

.;Gain of glycosylation at A255 (P = 0.0147);Gain of glycosylation at A255 (P = 0.0147);

MVP

0.31

MPC

0.47

ClinPred

0.16

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.45

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over