rs2152143

Variant names:

• chr10-128108716-C-T
• rs2152143
• NM_002417.5:c.3124G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3894 hom., cov: 33)
  • Exomes 𝑓: 0.24 (43598 hom.)
• Consequence: MKI67 NM_002417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	NM_002417.5	MANE Select	c.3124G>A	p.Gly1042Ser	missense	Exon 13 of 15	NP_002408.3
	MKI67	NM_001145966.2		c.2044G>A	p.Gly682Ser	missense	Exon 12 of 14	NP_001139438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	ENST00000368654.8	TSL:2 MANE Select	c.3124G>A	p.Gly1042Ser	missense	Exon 13 of 15	ENSP00000357643.3
	MKI67	ENST00000935442.1		c.3118G>A	p.Gly1040Ser	missense	Exon 13 of 15	ENSP00000605501.1
	MKI67	ENST00000368653.7	TSL:2	c.2044G>A	p.Gly682Ser	missense	Exon 12 of 14	ENSP00000357642.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32677 AN: 152038 Hom.: 3886 Cov.: 33

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

GnomAD2 exomes AF: 0.245 AC: 61483 AN: 251406 AF XY: 0.243

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 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.: 78 AF XY: 0.241 AC XY: 175463 AN XY: 727236

African (AFR) AF: 0.121 AC: 4066 AN: 33480

American (AMR) AF: 0.321 AC: 14335 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7781 AN: 26136

East Asian (EAS) AF: 0.159 AC: 6317 AN: 39700

South Asian (SAS) AF: 0.210 AC: 18154 AN: 86258

European-Finnish (FIN) AF: 0.291 AC: 15563 AN: 53418

Middle Eastern (MID) AF: 0.270 AC: 1558 AN: 5768

European-Non Finnish (NFE) AF: 0.244 AC: 271432 AN: 1111992

Other (OTH) AF: 0.235 AC: 14218 AN: 60396

GnomAD4 genome AF: 0.215 AC: 32696 AN: 152156 Hom.: 3894 Cov.: 33 AF XY: 0.217 AC XY: 16168 AN XY: 74392

African (AFR) AF: 0.128 AC: 5327 AN: 41522

American (AMR) AF: 0.277 AC: 4244 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.128 AC: 660 AN: 5160

South Asian (SAS) AF: 0.203 AC: 978 AN: 4822

European-Finnish (FIN) AF: 0.294 AC: 3108 AN: 10574

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16449 AN: 67992

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.237 Hom.: 15915

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.85	T
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	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		-1.4
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.053
Sift	Benign	0.81	T
Sift4G	Benign	0.63	T
Polyphen		0.97	D
Vest4		0.030
MPC		0.25
ClinPred		0.0023	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.074
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2152143; hg19: chr10-129906980; COSMIC: COSV64072293; COSMIC: COSV64072293;