rs10082391

Variant names:

• chr10-128103561-T-C
• rs10082391
• NM_002417.5:c.8279A>G

Variant summary

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

The NM_002417.5(MKI67):​c.8279A>G​(p.Asp2760Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,804 control chromosomes in the GnomAD database, including 28,237 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.22 (3891 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24346 hom.)
• Consequence: MKI67 NM_002417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 21 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=0.0054243207).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKI67	NM_002417.5	c.8279A>G	p.Asp2760Gly	missense_variant	Exon 13 of 15	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2	c.7199A>G	p.Asp2400Gly	missense_variant	Exon 12 of 14		NP_001139438.1
MKI67	XM_011539818.3	c.7247A>G	p.Asp2416Gly	missense_variant	Exon 10 of 12		XP_011538120.1
MKI67	XM_006717864.4	c.5957A>G	p.Asp1986Gly	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.8279A>G	p.Asp2760Gly	missense_variant	Exon 13 of 15	2	NM_002417.5	ENSP00000357643.3
MKI67	ENST00000368653.7	c.7199A>G	p.Asp2400Gly	missense_variant	Exon 12 of 14	2		ENSP00000357642.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32865 AN: 151818 Hom.: 3892 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.190 AC: 47680 AN: 251194 AF XY: 0.183

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.179 AC: 262280 AN: 1461868 Hom.: 24346 Cov.: 78 AF XY: 0.177 AC XY: 129011 AN XY: 727236

African (AFR) AF: 0.313 AC: 10481 AN: 33478

American (AMR) AF: 0.224 AC: 10034 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5337 AN: 26136

East Asian (EAS) AF: 0.275 AC: 10923 AN: 39700

South Asian (SAS) AF: 0.141 AC: 12147 AN: 86254

European-Finnish (FIN) AF: 0.128 AC: 6819 AN: 53418

Middle Eastern (MID) AF: 0.165 AC: 951 AN: 5768

European-Non Finnish (NFE) AF: 0.175 AC: 194230 AN: 1111996

Other (OTH) AF: 0.188 AC: 11358 AN: 60394

GnomAD4 genome AF: 0.216 AC: 32881 AN: 151936 Hom.: 3891 Cov.: 32 AF XY: 0.215 AC XY: 15941 AN XY: 74298

African (AFR) AF: 0.314 AC: 13001 AN: 41382

American (AMR) AF: 0.226 AC: 3454 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3462

East Asian (EAS) AF: 0.269 AC: 1385 AN: 5152

South Asian (SAS) AF: 0.138 AC: 665 AN: 4818

European-Finnish (FIN) AF: 0.125 AC: 1326 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11621 AN: 67950

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.190 Hom.: 9833

Bravo AF: 0.227

TwinsUK AF: 0.172 AC: 638

ALSPAC AF: 0.181 AC: 698

ESP6500AA AF: 0.308 AC: 1359

ESP6500EA AF: 0.174 AC: 1493

ExAC AF: 0.188 AC: 22821

Asia WGS AF: 0.242 AC: 845 AN: 3478

EpiCase AF: 0.175

EpiControl AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0072	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.94	.;L
PhyloP100		-0.36
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Benign	0.15	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.99	D;P
Vest4		0.14
MPC		0.065
ClinPred		0.014	T
GERP RS		-2.4
Varity_R		0.052
gMVP		0.061
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: rs10082391; hg19: chr10-129901825; COSMIC: COSV64073322; COSMIC: COSV64073322;