10-128100626-T-C

Variant names:

• chr10-128100626-T-C
• rs3781305
• NM_002417.5:c.9705+632A>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.9705+632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,070 control chromosomes in the GnomAD database, including 14,509 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 0.44 (14509 hom., cov: 33)
• Consequence: MKI67 NM_002417.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 1 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKI67	NM_002417.5	c.9705+632A>G		intron_variant	Intron 14 of 14	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2	c.8625+632A>G		intron_variant	Intron 13 of 13		NP_001139438.1
MKI67	XM_011539818.3	c.8673+632A>G		intron_variant	Intron 11 of 11		XP_011538120.1
MKI67	XM_006717864.4	c.7383+632A>G		intron_variant	Intron 3 of 3		XP_006717927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKI67	ENST00000368654.8	c.9705+632A>G		intron_variant	Intron 14 of 14	2	NM_002417.5	ENSP00000357643.3
MKI67	ENST00000368653.7	c.8625+632A>G		intron_variant	Intron 13 of 13	2		ENSP00000357642.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66188 AN: 151952 Hom.: 14504 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66221 AN: 152070 Hom.: 14509 Cov.: 33 AF XY: 0.437 AC XY: 32478 AN XY: 74382

African (AFR) AF: 0.440 AC: 18240 AN: 41446

American (AMR) AF: 0.504 AC: 7706 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2123 AN: 5164

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4826

European-Finnish (FIN) AF: 0.440 AC: 4661 AN: 10582

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28474 AN: 67986

Other (OTH) AF: 0.456 AC: 962 AN: 2108

Alfa AF: 0.439 Hom.: 18621

Bravo AF: 0.445

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0080
DANN	Benign	0.70
PhyloP100		-1.4
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: rs3781305; hg19: chr10-129898890;