NM_033286.4:c.71_72delCCinsTT

Variant names:

• chr15-40382906-CC-TT
• NM_033286.4:c.71_72delCCinsTT
• KNSTRN p.Ser24Phe

Variant summary

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

The NM_033286.4(KNSTRN):​c.71_72delCCinsTT​(p.Ser24Phe) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KNSTRN NM_033286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 1 publications found

Genes affected

KNSTRN (HGNC:30767): (kinetochore localized astrin (SPAG5) binding protein) Enables microtubule plus-end binding activity and protein homodimerization activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; mitotic sister chromatid segregation; and regulation of attachment of spindle microtubules to kinetochore. Located in several cellular components, including kinetochore; microtubule cytoskeleton; and ruffle. Implicated in actinic keratosis and skin squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033286.4. 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
	KNSTRN	NM_033286.4	MANE Select	c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	NP_150628.3	Q9Y448-1
	KNSTRN	NM_001142761.1		c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	NP_001136233.1	Q9Y448-2
	KNSTRN	NM_001142762.1		c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	NP_001136234.1	Q9Y448-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNSTRN	ENST00000249776.13	TSL:1 MANE Select	c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	ENSP00000249776.8	Q9Y448-1
	KNSTRN	ENST00000416151.6	TSL:3	c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	ENSP00000391233.2	Q9Y448-2
	KNSTRN	ENST00000448395.6	TSL:2	c.71_72delCCinsTT	p.Ser24Phe	missense	N/A	ENSP00000393001.2	Q9Y448-3

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
PhyloP100		-0.17

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: chr15-40675107;

COSMIC: COSV51107911;

COSMIC: COSV51107911;