NM_004523.4:c.868C>T

Variant names:

• chr10-92613455-C-T
• rs1554859966
• NM_004523.4:c.868C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_004523.4(KIF11):​c.868C>T​(p.Gln290*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF11 NM_004523.4 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.07
• Publications: 1 publications found

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-92613455-C-T is Pathogenic according to our data. Variant chr10-92613455-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 435617.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004523.4. 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
	KIF11	NM_004523.4	MANE Select	c.868C>T	p.Gln290*	stop_gained	Exon 8 of 22	NP_004514.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000260731.5	TSL:1 MANE Select	c.868C>T	p.Gln290*	stop_gained	Exon 8 of 22	ENSP00000260731.3
	KIF11	ENST00000676647.1		c.661C>T	p.Gln221*	stop_gained	Exon 8 of 22	ENSP00000503394.1
	KIF11	ENST00000676757.1		c.661C>T	p.Gln221*	stop_gained	Exon 8 of 22	ENSP00000504289.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability Pathogenic:1

Mar 15, 2017

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		6.1
Vest4		0.89
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=2/198	disease causing (ClinVar)

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: rs1554859966; hg19: chr10-94373212; COSMIC: COSV53272962;