Variant rs4267943 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018132.4(CENPQ):c.187G>A(p.Gly63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,610,876 control chromosomes in the GnomAD database, including 106,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 9957 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96198 hom. )

Consequence

CENPQ
NM_018132.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.800

Variant links:

Genes affected

CENPQ (HGNC:21347): (centromere protein Q) CENPQ 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]

CENPQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023818016).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPQ	NM_018132.4 linkuse as main transcript	c.187G>A	p.Gly63Arg	missense_variant	4/9	ENST00000335783.4	NP_060602.2	Q7L2Z9
CENPQ	XM_005249205.2 linkuse as main transcript	c.187G>A	p.Gly63Arg	missense_variant	4/9		XP_005249262.1	Q7L2Z9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPQ	ENST00000335783.4 linkuse as main transcript	c.187G>A	p.Gly63Arg	missense_variant	4/9	1	NM_018132.4	ENSP00000337289.2		Q7L2Z9

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54400

AN:

151742

Hom.:

9942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.332

AC:

82698

AN:

249384

Hom.:

14501

AF XY:

0.335

AC XY:

45119

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.360

AC:

525407

AN:

1459014

Hom.:

96198

Cov.:

AF XY:

0.359

AC XY:

260783

AN XY:

725766

show subpopulations

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.359

AC:

54449

AN:

151862

Hom.:

9957

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.373

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.352

Hom.:

22366

Bravo

AF:

0.346

TwinsUK

AF:

0.384

AC:

1423

ALSPAC

AF:

0.364

AC:

1404

ESP6500AA

AF:

0.391

AC:

1724

ESP6500EA

AF:

0.367

AC:

3158

ExAC

AF:

0.341

AC:

41407

Asia WGS

AF:

0.341

AC:

1189

AN:

3476

EpiCase

AF:

0.345

EpiControl

AF:

0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

DANN

Benign

0.75

DEOGEN2

Benign

0.010

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.22

REVEL

Benign

0.061

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0040

Polyphen

0.0030

Vest4

0.060

MutPred

0.093

Gain of solvent accessibility (P = 0.0584);

MPC

0.019

ClinPred

0.0031

GERP RS

-6.5

Varity_R

0.042

gMVP

0.094

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over