chr6-49472092-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 58 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPQ	NM_018132.4	MANE Select	c.187G>A	p.Gly63Arg	missense	Exon 4 of 9	NP_060602.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPQ	ENST00000335783.4	TSL:1 MANE Select	c.187G>A	p.Gly63Arg	missense	Exon 4 of 9	ENSP00000337289.2	Q7L2Z9
	CENPQ	ENST00000868052.1		c.187G>A	p.Gly63Arg	missense	Exon 4 of 9	ENSP00000538111.1
	CENPQ	ENST00000935104.1		c.187G>A	p.Gly63Arg	missense	Exon 4 of 10	ENSP00000605163.1

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

GnomAD2 exomes AF: 0.332 AC: 82698 AN: 249384 AF XY: 0.335

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

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

GnomAD4 genome AF: 0.359 AC: 54449 AN: 151862 Hom.: 9957 Cov.: 32 AF XY: 0.355 AC XY: 26374 AN XY: 74218

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: 64 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25070 AN: 67880

Other (OTH) AF: 0.330 AC: 693 AN: 2100

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 v4.9

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
PhyloP100		-0.80
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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