Variant rs1056787 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000273853.11(CENPC):c.1166G>A(p.Gly389Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 1,612,198 control chromosomes in the GnomAD database, including 5,776 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.057 ( 329 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5447 hom. )

Consequence

CENPC
ENST00000273853.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Variant links:

Genes affected

CENPC (HGNC:1854): (centromere protein C) Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

CENPC 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=0.002503246).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPC	NM_001812.4 linkuse as main transcript	c.1166G>A	p.Gly389Asp	missense_variant	8/19	ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11 linkuse as main transcript	c.1166G>A	p.Gly389Asp	missense_variant	8/19	1	NM_001812.4	ENSP00000273853	P1	Q03188-1
CENPC	ENST00000510189.5 linkuse as main transcript	n.1314G>A		non_coding_transcript_exon_variant	8/14	1
CENPC	ENST00000506882.5 linkuse as main transcript	c.1166G>A	p.Gly389Asp	missense_variant, NMD_transcript_variant	8/20	1		ENSP00000426078		Q03188-2
CENPC	ENST00000513216.5 linkuse as main transcript	c.887G>A	p.Gly296Asp	missense_variant, NMD_transcript_variant	4/15	5		ENSP00000421234

Frequencies

GnomAD3 genomes

AF:

0.0566

AC:

8606

AN:

152068

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0530

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0888

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0579

AC:

14329

AN:

247656

Hom.:

518

AF XY:

0.0579

AC XY:

7779

AN XY:

134354

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.0374

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0543

Gnomad NFE exome

AF:

0.0930

Gnomad OTH exome

AF:

0.0665

GnomAD4 exome

AF:

0.0812

AC:

118532

AN:

1460012

Hom.:

5447

Cov.:

AF XY:

0.0790

AC XY:

57400

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.0378

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0543

Gnomad4 NFE exome

AF:

0.0959

Gnomad4 OTH exome

AF:

0.0715

GnomAD4 genome

AF:

0.0565

AC:

8601

AN:

152186

Hom.:

329

Cov.:

AF XY:

0.0538

AC XY:

3999

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0529

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0550

Gnomad4 NFE

AF:

0.0888

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0807

Hom.:

1023

Bravo

AF:

0.0556

TwinsUK

AF:

0.0987

AC:

366

ALSPAC

AF:

0.108

AC:

415

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.0903

AC:

737

ExAC

AF:

0.0595

AC:

7183

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.6

DANN

Benign

0.37

DEOGEN2

Benign

0.026

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

1.8

REVEL

Benign

0.045

Sift

Benign

1.0

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.031

MPC

0.050

ClinPred

0.0014

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.019

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