16-67833836-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8G) has been classified as Likely 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

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

short stature and microcephaly with genital anomalies
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CENPT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPT	NM_025082.4	MANE Select	c.24C>A	p.Ser8Arg	missense	Exon 4 of 16	NP_079358.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CENPT	ENST00000562787.6	TSL:2 MANE Select	c.24C>A	p.Ser8Arg	missense	Exon 4 of 16	ENSP00000457810.1
CENPT	ENST00000937858.1		c.24C>A	p.Ser8Arg	missense	Exon 1 of 14	ENSP00000607917.1
CENPT	ENST00000937857.1		c.24C>A	p.Ser8Arg	missense	Exon 1 of 14	ENSP00000607916.1

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

GnomAD2 exomes

AF:

0.0302

AC:

5809

AN:

192428

AF XY:

0.0311

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 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

African (AFR)

AF:

0.00858

AC:

263

AN:

30656

American (AMR)

AF:

0.0235

AC:

892

AN:

37976

Ashkenazi Jewish (ASJ)

AF:

0.0589

AC:

1457

AN:

24748

East Asian (EAS)

AF:

0.0000288

AC:

AN:

34764

South Asian (SAS)

AF:

0.0113

AC:

919

AN:

81286

European-Finnish (FIN)

AF:

0.0274

AC:

1399

AN:

51096

Middle Eastern (MID)

AF:

0.0980

AC:

551

AN:

5620

European-Non Finnish (NFE)

AF:

0.0418

AC:

45591

AN:

1091552

Other (OTH)

AF:

0.0396

AC:

2309

AN:

58312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

2397

4794

7191

9588

11985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1700

3400

5100

6800

8500

<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

AF:

0.0292

AC:

4442

AN:

152320

Hom.:

Cov.:

AF XY:

0.0276

AC XY:

2059

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00924

AC:

384

AN:

41566

American (AMR)

AF:

0.0351

AC:

537

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

188

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00911

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0252

AC:

268

AN:

10628

Middle Eastern (MID)

AF:

0.158

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0416

AC:

2827

AN:

68016

Other (OTH)

AF:

0.0444

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

232

464

697

929

1161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0391

Hom.:

343

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

CENPT-related disorder (1)

not provided (1)

Short stature and microcephaly with genital anomalies (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.7

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

-0.098

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

REVEL

Benign

0.066

Sift

Benign

0.089

Sift4G

Benign

0.12

Polyphen

0.0070

Vest4

0.064

MutPred

0.094

Loss of phosphorylation at S8 (P = 0.0096)

MPC

0.10

ClinPred

0.0059

GERP RS

1.2

PromoterAI

0.079

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.084

gMVP

0.12

Mutation Taster

=296/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over