chr10-128101314-T-C

Variant names:

• chr10-128101314-T-C
• rs8473
• NM_002417.5:c.9649A>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.9649A>G​(p.Lys3217Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,613,866 control chromosomes in the GnomAD database, including 214,248 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 0.50 (19138 hom., cov: 34)
  • Exomes 𝑓: 0.52 (195110 hom.)
• Consequence: MKI67 NM_002417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 40 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=8.121955E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 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.9649A>G	p.Lys3217Glu	missense	Exon 14 of 15	NP_002408.3
	MKI67	NM_001145966.2		c.8569A>G	p.Lys2857Glu	missense	Exon 13 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.9649A>G	p.Lys3217Glu	missense	Exon 14 of 15	ENSP00000357643.3
	MKI67	ENST00000935442.1		c.9643A>G	p.Lys3215Glu	missense	Exon 14 of 15	ENSP00000605501.1
	MKI67	ENST00000368653.7	TSL:2	c.8569A>G	p.Lys2857Glu	missense	Exon 13 of 14	ENSP00000357642.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75960 AN: 152020 Hom.: 19137 Cov.: 34

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.524

GnomAD2 exomes AF: 0.508 AC: 127625 AN: 251464 AF XY: 0.502

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.407

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.515 AC: 753278 AN: 1461728 Hom.: 195110 Cov.: 63 AF XY: 0.512 AC XY: 372613 AN XY: 727158

African (AFR) AF: 0.455 AC: 15242 AN: 33480

American (AMR) AF: 0.595 AC: 26594 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 15063 AN: 26132

East Asian (EAS) AF: 0.443 AC: 17600 AN: 39700

South Asian (SAS) AF: 0.421 AC: 36285 AN: 86254

European-Finnish (FIN) AF: 0.486 AC: 25979 AN: 53406

Middle Eastern (MID) AF: 0.518 AC: 2986 AN: 5768

European-Non Finnish (NFE) AF: 0.524 AC: 582984 AN: 1111874

Other (OTH) AF: 0.506 AC: 30545 AN: 60390

GnomAD4 genome AF: 0.499 AC: 75988 AN: 152138 Hom.: 19138 Cov.: 34 AF XY: 0.498 AC XY: 37012 AN XY: 74386

African (AFR) AF: 0.465 AC: 19318 AN: 41500

American (AMR) AF: 0.558 AC: 8543 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2079 AN: 5174

South Asian (SAS) AF: 0.406 AC: 1958 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5041 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35192 AN: 67988

Other (OTH) AF: 0.523 AC: 1101 AN: 2106

Alfa AF: 0.520 Hom.: 71846

Bravo AF: 0.509

TwinsUK AF: 0.518 AC: 1920

ALSPAC AF: 0.537 AC: 2070

ESP6500AA AF: 0.464 AC: 2045

ESP6500EA AF: 0.525 AC: 4511

ExAC AF: 0.501 AC: 60891

Asia WGS AF: 0.433 AC: 1507 AN: 3478

EpiCase AF: 0.526

EpiControl AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.12
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0000081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.51
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.039
MPC		0.052
ClinPred		0.0049	T
GERP RS		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.013
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: rs8473; hg19: chr10-129899578; COSMIC: COSV64073880; COSMIC: COSV64073880;