NM_002417.5:c.9684G>A

Variant names:

• chr10-128101279-C-T
• rs10082504
• NM_002417.5:c.9684G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002417.5(MKI67):​c.9684G>A​(p.Arg3228Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 1,613,648 control chromosomes in the GnomAD database, including 8,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.090 (685 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7508 hom.)
• Consequence: MKI67 NM_002417.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 12 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.049 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	NM_002417.5	MANE Select	c.9684G>A	p.Arg3228Arg	synonymous	Exon 14 of 15	NP_002408.3
	MKI67	NM_001145966.2		c.8604G>A	p.Arg2868Arg	synonymous	Exon 13 of 14	NP_001139438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	ENST00000368654.8	TSL:2 MANE Select	c.9684G>A	p.Arg3228Arg	synonymous	Exon 14 of 15	ENSP00000357643.3
	MKI67	ENST00000368653.7	TSL:2	c.8604G>A	p.Arg2868Arg	synonymous	Exon 13 of 14	ENSP00000357642.3
	MKI67	ENST00000464771.1	TSL:3	n.*205G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13763 AN: 152198 Hom.: 684 Cov.: 33

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0960

GnomAD2 exomes AF: 0.107 AC: 26921 AN: 251266 AF XY: 0.106

Gnomad AFR exome AF: 0.0678

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.144

Gnomad FIN exome AF: 0.0635

Gnomad NFE exome AF: 0.0968

Gnomad OTH exome AF: 0.0946

GnomAD4 exome AF: 0.0983 AC: 143627 AN: 1461332 Hom.: 7508 Cov.: 32 AF XY: 0.0986 AC XY: 71654 AN XY: 726922

African (AFR) AF: 0.0640 AC: 2141 AN: 33474

American (AMR) AF: 0.163 AC: 7280 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2681 AN: 26126

East Asian (EAS) AF: 0.133 AC: 5266 AN: 39688

South Asian (SAS) AF: 0.115 AC: 9940 AN: 86238

European-Finnish (FIN) AF: 0.0638 AC: 3406 AN: 53410

Middle Eastern (MID) AF: 0.0824 AC: 475 AN: 5764

European-Non Finnish (NFE) AF: 0.0962 AC: 106875 AN: 1111536

Other (OTH) AF: 0.0921 AC: 5563 AN: 60374

GnomAD4 genome AF: 0.0903 AC: 13755 AN: 152316 Hom.: 685 Cov.: 33 AF XY: 0.0910 AC XY: 6778 AN XY: 74486

African (AFR) AF: 0.0689 AC: 2863 AN: 41568

American (AMR) AF: 0.137 AC: 2094 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3472

East Asian (EAS) AF: 0.136 AC: 702 AN: 5180

South Asian (SAS) AF: 0.109 AC: 527 AN: 4830

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6307 AN: 68026

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0825 Hom.: 313

Bravo AF: 0.0956

Asia WGS AF: 0.126 AC: 441 AN: 3478

EpiCase AF: 0.0966

EpiControl AF: 0.0944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs10082504; hg19: chr10-129899543; COSMIC: COSV64073354; COSMIC: COSV64073354;