Variant rs1063535 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.7823C>T(p.Pro2608Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,566 control chromosomes in the GnomAD database, including 210,415 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 0.50 ( 18779 hom., cov: 31)

Exomes 𝑓: 0.51 ( 191636 hom. )

Consequence

MKI67
NM_002417.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.821

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=1.1872851E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MKI67	NM_002417.5 linkuse as main transcript	c.7823C>T	p.Pro2608Leu	missense_variant	13/15	ENST00000368654.8
MKI67	NM_001145966.2 linkuse as main transcript	c.6743C>T	p.Pro2248Leu	missense_variant	12/14
MKI67	XM_011539818.3 linkuse as main transcript	c.6791C>T	p.Pro2264Leu	missense_variant	10/12
MKI67	XM_006717864.4 linkuse as main transcript	c.5501C>T	p.Pro1834Leu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKI67	ENST00000368654.8 linkuse as main transcript	c.7823C>T	p.Pro2608Leu	missense_variant	13/15	2	NM_002417.5	P2	P46013-1
MKI67	ENST00000368653.7 linkuse as main transcript	c.6743C>T	p.Pro2248Leu	missense_variant	12/14	2		A2	P46013-2

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75173

AN:

151630

Hom.:

18778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.524

GnomAD3 exomes

AF:

0.504

AC:

126572

AN:

251370

Hom.:

32463

AF XY:

0.498

AC XY:

67630

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.403

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.475

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.511

AC:

746570

AN:

1461818

Hom.:

191636

Cov.:

AF XY:

0.508

AC XY:

369270

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.594

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.496

AC:

75203

AN:

151748

Hom.:

18779

Cov.:

AF XY:

0.494

AC XY:

36602

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.513

Gnomad4 OTH

AF:

0.522

Alfa

AF:

0.517

Hom.:

50437

Bravo

AF:

0.504

TwinsUK

AF:

0.513

AC:

1903

ALSPAC

AF:

0.533

AC:

2054

ESP6500AA

AF:

0.459

AC:

2021

ESP6500EA

AF:

0.520

AC:

4473

ExAC

AF:

0.497

AC:

60304

Asia WGS

AF:

0.430

AC:

1498

AN:

3478

EpiCase

AF:

0.522

EpiControl

AF:

0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.19

DANN

Benign

0.51

DEOGEN2

Benign

0.0021

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

0.73

N;N

REVEL

Benign

0.011

Sift

Benign

0.46

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0

B;B

Vest4

0.090

MPC

0.043

ClinPred

0.0022

GERP RS

-4.0

Varity_R

0.016

gMVP

0.020

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