Variant rs3740423 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.4208A>T(p.Glu1403Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,910 control chromosomes in the GnomAD database, including 27,230 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.14 ( 2063 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25167 hom. )

Consequence

MKI67
NM_002417.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.592

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005635649).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MKI67	NM_002417.5 linkuse as main transcript	c.4208A>T	p.Glu1403Val	missense_variant	13/15	ENST00000368654.8
MKI67	NM_001145966.2 linkuse as main transcript	c.3128A>T	p.Glu1043Val	missense_variant	12/14
MKI67	XM_011539818.3 linkuse as main transcript	c.3176A>T	p.Glu1059Val	missense_variant	10/12
MKI67	XM_006717864.4 linkuse as main transcript	c.1886A>T	p.Glu629Val	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKI67	ENST00000368654.8 linkuse as main transcript	c.4208A>T	p.Glu1403Val	missense_variant	13/15	2	NM_002417.5	P2	P46013-1
MKI67	ENST00000368653.7 linkuse as main transcript	c.3128A>T	p.Glu1043Val	missense_variant	12/14	2		A2	P46013-2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22000

AN:

151908

Hom.:

2056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0342

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.195

AC:

48916

AN:

251414

Hom.:

5369

AF XY:

0.195

AC XY:

26446

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.182

AC:

265511

AN:

1461884

Hom.:

25167

Cov.:

AF XY:

0.183

AC XY:

132909

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.145

AC:

22008

AN:

152026

Hom.:

2063

Cov.:

AF XY:

0.148

AC XY:

11014

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0341

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.155

Hom.:

733

Bravo

AF:

0.143

TwinsUK

AF:

0.180

AC:

669

ALSPAC

AF:

0.180

AC:

692

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.183

AC:

1574

ExAC

AF:

0.189

AC:

22920

Asia WGS

AF:

0.143

AC:

496

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.022

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.14

MPC

0.30

ClinPred

0.029

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.23

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