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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKI67	NM_002417.5	c.3124G>A	p.Gly1042Ser	missense_variant	Exon 13 of 15	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2	c.2044G>A	p.Gly682Ser	missense_variant	Exon 12 of 14		NP_001139438.1
MKI67	XM_011539818.3	c.2092G>A	p.Gly698Ser	missense_variant	Exon 10 of 12		XP_011538120.1
MKI67	XM_006717864.4	c.802G>A	p.Gly268Ser	missense_variant	Exon 2 of 4		XP_006717927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKI67	ENST00000368654.8	c.3124G>A	p.Gly1042Ser	missense_variant	Exon 13 of 15	2	NM_002417.5	ENSP00000357643.3
MKI67	ENST00000368653.7	c.2044G>A	p.Gly682Ser	missense_variant	Exon 12 of 14	2		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

Gnomad4 AFR exome AF: 0.121 AC: 4066 AN: 33480

Gnomad4 AMR exome AF: 0.321 AC: 14335 AN: 44724

Gnomad4 ASJ exome AF: 0.298 AC: 7781 AN: 26136

Gnomad4 EAS exome AF: 0.159 AC: 6317 AN: 39700

Gnomad4 SAS exome AF: 0.210 AC: 18154 AN: 86258

Gnomad4 FIN exome AF: 0.291 AC: 15563 AN: 53418

Gnomad4 NFE exome AF: 0.244 AC: 271432 AN: 1111992

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.128 AC: 0.128293 AN: 0.128293

Gnomad4 AMR AF: 0.277 AC: 0.277458 AN: 0.277458

Gnomad4 ASJ AF: 0.297 AC: 0.29683 AN: 0.29683

Gnomad4 EAS AF: 0.128 AC: 0.127907 AN: 0.127907

Gnomad4 SAS AF: 0.203 AC: 0.20282 AN: 0.20282

Gnomad4 FIN AF: 0.294 AC: 0.293929 AN: 0.293929

Gnomad4 NFE AF: 0.242 AC: 0.241926 AN: 0.241926

Gnomad4 OTH AF: 0.245 AC: 0.245033 AN: 0.245033

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 v4.3

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;T
MetaRNN	Benign	0.0051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	.;N
PrimateAI	Benign	0.20	T
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	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

Publications

LitVar

Other links and lift over

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