chr16-67828517-G-A

Position:

chr16-67828517-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_025082.4(CENPT):c.1519C>T(p.Arg507Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00198 in 1,614,148 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

CENPT
NM_025082.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.26

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:

CENPT (HGNC:):

CENPT links:

TSNAXIP1 (HGNC:18586): (translin associated factor X interacting protein 1) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TSNAXIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2796585).

BP6

Variant 16-67828517-G-A is Benign according to our data. Variant chr16-67828517-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3366379.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPT	NM_025082.4 linkuse as main transcript	c.1519C>T	p.Arg507Cys	missense_variant	15/16	ENST00000562787.6	NP_079358.3	Q96BT3-1B3KPB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPT	ENST00000562787.6 linkuse as main transcript	c.1519C>T	p.Arg507Cys	missense_variant	15/16	2	NM_025082.4	ENSP00000457810.1		Q96BT3-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

177

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00109

AC:

271

AN:

249528

Hom.:

AF XY:

0.00112

AC XY:

151

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000650

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00207

AC:

3026

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1417

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00258

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152278

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000728

AC:

ESP6500EA

AF:

0.00154

AC:

ExAC

AF:

0.00111

AC:

134

EpiCase

AF:

0.00213

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 08, 2024

Variant summary: CENPT c.1519C>T (p.Arg507Cys) results in a non-conservative amino acid change located in the CENP-T/Histone H4, histone fold domain (IPR035425) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.002 in 1614148 control chromosomes, predominantly at a frequency of 0.0026 within the Non-Finnish European subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in CENPT causing the Short Stature And Microcephaly With Genital Anomalies phenotype. To our knowledge, no occurrence of c.1519C>T in individuals affected with Short Stature And Microcephaly With Genital Anomalies and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Pathogenic

0.84

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.2

D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.026

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.87

MVP

0.97

MPC

0.47

ClinPred

0.075

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.87

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