rs4267943

Variant names:

• chr6-49472092-G-A
• rs4267943
• NM_018132.4:c.187G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (9957 hom., cov: 32)
  • Exomes 𝑓: 0.36 (96198 hom.)
• Consequence: CENPQ NM_018132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CENPQ	NM_018132.4	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 9	ENST00000335783.4	NP_060602.2
CENPQ	XM_005249205.2	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 9		XP_005249262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPQ	ENST00000335783.4	c.187G>A	p.Gly63Arg	missense_variant	Exon 4 of 9	1	NM_018132.4	ENSP00000337289.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54400 AN: 151742 Hom.: 9942 Cov.: 32

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

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.: 34 AF XY: 0.359 AC XY: 260783 AN XY: 725766

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.: 32 AF XY: 0.355 AC XY: 26374 AN XY: 74218

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	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.75
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.061
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.0030	B
Vest4		0.060
MutPred		0.093		Gain of solvent accessibility (P = 0.0584);
MPC		0.019
ClinPred		0.0031	T
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

Other links and lift over

dbSNP: rs4267943; hg19: chr6-49439805; COSMIC: COSV59920658;