dbSNP rs4267943: CENPQ:p.Gly63Arg (chr6-49472092-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

58 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CENPQ	NM_018132.4 link	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 9	ENST00000335783.4	NP_060602.2	Q7L2Z9
CENPQ	XM_005249205.2 link	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 9		XP_005249262.1	Q7L2Z9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPQ	ENST00000335783.4 link	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.332

AC:

82698

AN:

249384

AF XY:

0.335

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 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

African (AFR)

AF:

0.393

AC:

13100

AN:

33364

American (AMR)

AF:

0.201

AC:

8962

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8639

AN:

26090

East Asian (EAS)

AF:

0.231

AC:

9126

AN:

39560

South Asian (SAS)

AF:

0.358

AC:

30695

AN:

85790

European-Finnish (FIN)

AF:

0.370

AC:

19674

AN:

53238

Middle Eastern (MID)

AF:

0.265

AC:

1527

AN:

5756

European-Non Finnish (NFE)

AF:

0.372

AC:

412743

AN:

1110458

Other (OTH)

AF:

0.347

AC:

20941

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15442

30884

46327

61769

77211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13078

26156

39234

52312

65390

<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:

0.359

AC:

54449

AN:

151862

Hom.:

9957

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.394

AC:

16312

AN:

41440

American (AMR)

AF:

0.257

AC:

3916

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1213

AN:

3466

East Asian (EAS)

AF:

0.222

AC:

1145

AN:

5168

South Asian (SAS)

AF:

0.373

AC:

1798

AN:

4818

European-Finnish (FIN)

AF:

0.373

AC:

3932

AN:

10536

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25070

AN:

67880

Other (OTH)

AF:

0.330

AC:

693

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1763

3526

5289

7052

8815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.354

Hom.:

31840

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

(source)

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

PhyloP100

-0.80

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over