rs11558534

Positions:

chr16-67833836-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025082.4(CENPT):c.24C>A(p.Ser8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,568,330 control chromosomes in the GnomAD database, including 1,273 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 96 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1177 hom. )

Consequence

CENPT
NM_025082.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

CENPT (HGNC:25787): (centromere protein T) The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

CENPT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020076036).

BP6

Variant 16-67833836-G-T is Benign according to our data. Variant chr16-67833836-G-T is described in ClinVar as [Benign]. Clinvar id is 1209722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPT	NM_025082.4 linkuse as main transcript	c.24C>A	p.Ser8Arg	missense_variant	4/16	ENST00000562787.6	NP_079358.3
CENPT	XM_047434686.1 linkuse as main transcript	c.24C>A	p.Ser8Arg	missense_variant	3/15		XP_047290642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPT	ENST00000562787.6 linkuse as main transcript	c.24C>A	p.Ser8Arg	missense_variant	4/16	2	NM_025082.4	ENSP00000457810	P1	Q96BT3-1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4445

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00924

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.0252

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0302

AC:

5809

AN:

192428

Hom.:

123

AF XY:

0.0311

AC XY:

3341

AN XY:

107268

show subpopulations

Gnomad AFR exome

AF:

0.00764

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0550

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0253

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0377

AC:

53382

AN:

1416010

Hom.:

1177

Cov.:

AF XY:

0.0372

AC XY:

26163

AN XY:

703228

show subpopulations

Gnomad4 AFR exome

AF:

0.00858

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0589

Gnomad4 EAS exome

AF:

0.0000288

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0292

AC:

4442

AN:

152320

Hom.:

Cov.:

AF XY:

0.0276

AC XY:

2059

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00924

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.0252

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0444

Alfa

AF:

0.0425

Hom.:

170

Bravo

AF:

0.0284

TwinsUK

AF:

0.0461

AC:

171

ALSPAC

AF:

0.0426

AC:

164

ESP6500AA

AF:

0.00845

AC:

ESP6500EA

AF:

0.0388

AC:

325

ExAC

AF:

0.0297

AC:

3562

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Short stature and microcephaly with genital anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

CENPT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.7

DANN

Benign

0.94

DEOGEN2

Benign

0.0088

T;T;.;T;.;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.51

.;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

N;N;.;N;N;D;D

REVEL

Benign

0.066

Sift

Benign

0.089

T;T;.;T;T;T;T

Sift4G

Benign

0.12

T;T;D;T;.;.;.

Polyphen

0.0070

B;B;.;.;.;.;.

Vest4

0.064

MutPred

0.094

Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);Loss of phosphorylation at S8 (P = 0.0096);

MPC

0.10

ClinPred

0.0059

GERP RS

1.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.084

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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