chr10-128103682-T-C

Variant names:

• chr10-128103682-T-C
• rs1050767
• NM_002417.5:c.8158A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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 Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MKI67 NM_002417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 25 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: Uncertain_significance. The variant received 0 ACMG points.

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

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.8158A>G	p.Thr2720Ala	missense	Exon 13 of 15	NP_002408.3
	MKI67	NM_001145966.2		c.7078A>G	p.Thr2360Ala	missense	Exon 12 of 14	NP_001139438.1	P46013-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	ENST00000368654.8	TSL:2 MANE Select	c.8158A>G	p.Thr2720Ala	missense	Exon 13 of 15	ENSP00000357643.3	P46013-1
	MKI67	ENST00000935442.1		c.8152A>G	p.Thr2718Ala	missense	Exon 13 of 15	ENSP00000605501.1
	MKI67	ENST00000368653.7	TSL:2	c.7078A>G	p.Thr2360Ala	missense	Exon 12 of 14	ENSP00000357642.3	P46013-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.24
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.037
Sift	Benign	0.30	T
Sift4G	Benign	0.23	T
Polyphen		0.77	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
Mutation Taster		=100/0	polymorphism

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: rs1050767; hg19: chr10-129901946;