rs8473

Variant names:

• chr10-128101314-T-A
• rs8473
• NM_002417.5:c.9649A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-128101314-T-A
• chr10-128101314-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002417.5(MKI67):​c.9649A>T​(p.Lys3217*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MKI67 NM_002417.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 40 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKI67	NM_002417.5	c.9649A>T	p.Lys3217*	stop_gained	Exon 14 of 15	ENST00000368654.8	NP_002408.3
MKI67	NM_001145966.2	c.8569A>T	p.Lys2857*	stop_gained	Exon 13 of 14		NP_001139438.1
MKI67	XM_011539818.3	c.8617A>T	p.Lys2873*	stop_gained	Exon 11 of 12		XP_011538120.1
MKI67	XM_006717864.4	c.7327A>T	p.Lys2443*	stop_gained	Exon 3 of 4		XP_006717927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKI67	ENST00000368654.8	c.9649A>T	p.Lys3217*	stop_gained	Exon 14 of 15	2	NM_002417.5	ENSP00000357643.3
MKI67	ENST00000368653.7	c.8569A>T	p.Lys2857*	stop_gained	Exon 13 of 14	2		ENSP00000357642.3
MKI67	ENST00000464771.1	n.*170A>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	34
DANN	Benign	0.93
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.074	N
PhyloP100		-0.51
Vest4		0.29
GERP RS		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=132/68	disease causing (fs/PTC)

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: rs8473; hg19: chr10-129899578;