Variant 10-128101279-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002417.5(MKI67):c.9684G>A(p.Arg3228=) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Variant links:

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]

MKI67 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MKI67	NM_002417.5 linkuse as main transcript	c.9684G>A	p.Arg3228=	synonymous_variant	14/15	ENST00000368654.8
MKI67	NM_001145966.2 linkuse as main transcript	c.8604G>A	p.Arg2868=	synonymous_variant	13/14
MKI67	XM_011539818.3 linkuse as main transcript	c.8652G>A	p.Arg2884=	synonymous_variant	11/12
MKI67	XM_006717864.4 linkuse as main transcript	c.7362G>A	p.Arg2454=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKI67	ENST00000368654.8 linkuse as main transcript	c.9684G>A	p.Arg3228=	synonymous_variant	14/15	2	NM_002417.5	P2	P46013-1
MKI67	ENST00000368653.7 linkuse as main transcript	c.8604G>A	p.Arg2868=	synonymous_variant	13/14	2		A2	P46013-2

Frequencies

GnomAD3 genomes

AF:

0.0904

AC:

13763

AN:

152198

Hom.:

684

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.107

AC:

26921

AN:

251266

Hom.:

1615

AF XY:

0.106

AC XY:

14341

AN XY:

135784

show subpopulations

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 SAS exome

AF:

0.116

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.:

AF XY:

0.0986

AC XY:

71654

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.0640

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.0962

Gnomad4 OTH exome

AF:

0.0921

GnomAD4 genome

AF:

0.0903

AC:

13755

AN:

152316

Hom.:

685

Cov.:

AF XY:

0.0910

AC XY:

6778

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0689

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.0916

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.0629

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.0964

Alfa

AF:

0.0827

Hom.:

312

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over