5-65518502-TCG-CAA

Variant names:

• chr5-65518502-TCG-CAA
• NM_022145.5:c.781_783delCGAinsTTG
• CENPK p.Arg261Leu

Variant summary

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

The NM_022145.5(CENPK):​c.781_783delCGAinsTTG​(p.Arg261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R261Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CENPK NM_022145.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

CENPK (HGNC:29479): (centromere protein K) CENPK is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022145.5. 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
	CENPK	NM_022145.5	MANE Select	c.781_783delCGAinsTTG	p.Arg261Leu	missense	N/A	NP_071428.2
	CENPK	NM_001349367.2		c.787_789delCGAinsTTG	p.Arg263Leu	missense	N/A	NP_001336296.1
	CENPK	NM_001267038.2		c.781_783delCGAinsTTG	p.Arg261Leu	missense	N/A	NP_001253967.1	Q9BS16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPK	ENST00000396679.6	TSL:1 MANE Select	c.781_783delCGAinsTTG	p.Arg261Leu	missense	N/A	ENSP00000379911.1	Q9BS16
	CENPK	ENST00000242872.7	TSL:1	c.781_783delCGAinsTTG	p.Arg261Leu	missense	N/A	ENSP00000242872.3	Q9BS16
	CENPK	ENST00000514814.5	TSL:1	c.781_783delCGAinsTTG	p.Arg261Leu	missense	N/A	ENSP00000422421.1	Q9BS16

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
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-64814329;