rs1050767

Positions:

• chr10-128103682-T-C
• chr10-128103682-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002417.5(MKI67):​c.8158A>G​(p.Thr2720Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2720P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MKI67 NM_002417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07497582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKI67	NM_002417.5	c.8158A>G	p.Thr2720Ala	missense_variant	13/15	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2	c.7078A>G	p.Thr2360Ala	missense_variant	12/14		NP_001139438.1
MKI67	XM_011539818.3	c.7126A>G	p.Thr2376Ala	missense_variant	10/12		XP_011538120.1
MKI67	XM_006717864.4	c.5836A>G	p.Thr1946Ala	missense_variant	2/4		XP_006717927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKI67	ENST00000368654.8	c.8158A>G	p.Thr2720Ala	missense_variant	13/15	2	NM_002417.5	ENSP00000357643.3
MKI67	ENST00000368653.7	c.7078A>G	p.Thr2360Ala	missense_variant	12/14	2		ENSP00000357642.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.98
DANN	Benign	0.75
DEOGEN2	Benign	0.0094	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.037
Sift	Benign	0.30	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.77	P;P
Vest4		0.052
MutPred		0.41		.;Gain of helix (P = 6e-04);
MVP		0.15
MPC		0.13
ClinPred		0.083	T
GERP RS		-0.38
Varity_R		0.034
gMVP		0.036

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

Other links and lift over

dbSNP: rs1050767; hg19: chr10-129901946;