NM_002417.5:c.9705+632A>C

Variant names:

• chr10-128100626-T-G
• rs3781305
• NM_002417.5:c.9705+632A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002417.5(MKI67):​c.9705+632A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	NM_002417.5	MANE Select	c.9705+632A>C		intron	N/A	NP_002408.3
	MKI67	NM_001145966.2		c.8625+632A>C		intron	N/A	NP_001139438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKI67	ENST00000368654.8	TSL:2 MANE Select	c.9705+632A>C		intron	N/A	ENSP00000357643.3
	MKI67	ENST00000368653.7	TSL:2	c.8625+632A>C		intron	N/A	ENSP00000357642.3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0080
DANN	Benign	0.72
PhyloP100		-1.4

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;