GeneBe

rs10082504

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002417.5(MKI67):​c.9684G>T​(p.Arg3228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R3228K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MKI67
NM_002417.5 missense

Scores

1
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

12 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12532896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MKI67
NM_002417.5
MANE Select
c.9684G>Tp.Arg3228Ser
missense
Exon 14 of 15NP_002408.3
MKI67
NM_001145966.2
c.8604G>Tp.Arg2868Ser
missense
Exon 13 of 14NP_001139438.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MKI67
ENST00000368654.8
TSL:2 MANE Select
c.9684G>Tp.Arg3228Ser
missense
Exon 14 of 15ENSP00000357643.3
MKI67
ENST00000935442.1
c.9678G>Tp.Arg3226Ser
missense
Exon 14 of 15ENSP00000605501.1
MKI67
ENST00000368653.7
TSL:2
c.8604G>Tp.Arg2868Ser
missense
Exon 13 of 14ENSP00000357642.3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
313
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.97
L
PhyloP100
-0.049
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.061
Sift
Uncertain
0.017
D
Sift4G
Benign
0.20
T
Polyphen
1.0
D
Vest4
0.29
MutPred
0.18
Loss of helix (P = 0.028)
MVP
0.29
MPC
0.22
ClinPred
0.60
D
GERP RS
-0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.073
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs10082504; hg19: chr10-129899543; API