Variant rs2152143 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002417.5(MKI67):c.3124G>A(p.Gly1042Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,614,028 control chromosomes in the GnomAD database, including 47,492 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 0.21 ( 3894 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43598 hom. )

Consequence

MKI67
NM_002417.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

MKI67 (HGNC:7107): (marker of proliferation Ki-67) Enables protein C-terminus binding activity. Involved in regulation of chromosome segregation and regulation of mitotic nuclear division. Located in chromosome; nuclear body; and nucleolus. Colocalizes with condensed chromosome. Implicated in Crohn's disease; breast cancer; human immunodeficiency virus infectious disease; and pancreatic cancer. Biomarker of several diseases, including Barrett's esophagus; autoimmune disease of musculoskeletal system (multiple); endocrine gland cancer (multiple); gastrointestinal system cancer (multiple); and interstitial cystitis. [provided by Alliance of Genome Resources, Apr 2022]

MKI67 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=0.0050908625).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MKI67	NM_002417.5 linkuse as main transcript	c.3124G>A	p.Gly1042Ser	missense_variant	13/15	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2 linkuse as main transcript	c.2044G>A	p.Gly682Ser	missense_variant	12/14		NP_001139438.1
MKI67	XM_011539818.3 linkuse as main transcript	c.2092G>A	p.Gly698Ser	missense_variant	10/12		XP_011538120.1
MKI67	XM_006717864.4 linkuse as main transcript	c.802G>A	p.Gly268Ser	missense_variant	2/4		XP_006717927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKI67	ENST00000368654.8 linkuse as main transcript	c.3124G>A	p.Gly1042Ser	missense_variant	13/15	2	NM_002417.5	ENSP00000357643	P2	P46013-1
MKI67	ENST00000368653.7 linkuse as main transcript	c.2044G>A	p.Gly682Ser	missense_variant	12/14	2		ENSP00000357642	A2	P46013-2

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32677

AN:

152038

Hom.:

3886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.245

AC:

61483

AN:

251406

Hom.:

8060

AF XY:

0.243

AC XY:

33017

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.242

AC:

353424

AN:

1461872

Hom.:

43598

Cov.:

AF XY:

0.241

AC XY:

175463

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.244

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.215

AC:

32696

AN:

152156

Hom.:

3894

Cov.:

AF XY:

0.217

AC XY:

16168

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.239

Hom.:

7794

Bravo

AF:

0.215

TwinsUK

AF:

0.238

AC:

883

ALSPAC

AF:

0.244

AC:

941

ESP6500AA

AF:

0.131

AC:

576

ESP6500EA

AF:

0.247

AC:

2128

ExAC

AF:

0.239

AC:

29014

Asia WGS

AF:

0.153

AC:

532

AN:

3478

EpiCase

AF:

0.251

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.24

DANN

Benign

0.88

DEOGEN2

Benign

0.0091

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.20

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.053

Sift

Benign

0.81

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.97

D;P

Vest4

0.030

MPC

0.25

ClinPred

0.0023

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.074

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