16-67828803-G-C

Position:

• chr16-67828803-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_025082.4(CENPT):​c.1321C>G​(p.Pro441Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,596,282 control chromosomes in the GnomAD database, including 8 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00050 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (7 hom.)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.793

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 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005937159).
• BP6: Variant 16-67828803-G-C is Benign according to our data. Variant chr16-67828803-G-C is described in ClinVar as [Benign]. Clinvar id is 3043796.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000511 (738/1443994) while in subpopulation EAS AF= 0.0165 (654/39654). AF 95% confidence interval is 0.0154. There are 7 homozygotes in gnomad4_exome. There are 373 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPT	NM_025082.4	c.1321C>G	p.Pro441Ala	missense_variant	14/16	ENST00000562787.6	NP_079358.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPT	ENST00000562787.6	c.1321C>G	p.Pro441Ala	missense_variant	14/16	2	NM_025082.4	ENSP00000457810.1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152170 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00101 AC: 230 AN: 227300 Hom.: 1 AF XY: 0.000951 AC XY: 118 AN XY: 124078

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000370

Gnomad ASJ exome AF: 0.000339

Gnomad EAS exome AF: 0.0126

Gnomad SAS exome AF: 0.000335

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.0000469

Gnomad OTH exome AF: 0.000548

GnomAD4 exome AF: 0.000511 AC: 738 AN: 1443994 Hom.: 7 Cov.: 33 AF XY: 0.000519 AC XY: 373 AN XY: 718478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000265

Gnomad4 ASJ exome AF: 0.000357

Gnomad4 EAS exome AF: 0.0165

Gnomad4 SAS exome AF: 0.000300

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000244

Gnomad4 OTH exome AF: 0.000352

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152288 Hom.: 1 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74460

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.000710

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00108 AC: 130

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CENPT-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 28, 2020

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.72	.;T;T
MetaRNN	Benign	0.0059	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.0070
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.25	T;T;T
Polyphen		0.094	B;B;.
Vest4		0.32
MVP		0.52
MPC		0.10
ClinPred		0.062	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.24

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

Other links and lift over

dbSNP: rs188159138; hg19: chr16-67862706; COSMIC: COSV54652085; COSMIC: COSV54652085;