rs797045650

Variant names:

• chr10-92609068-A-G
• rs797045650
• NM_004523.4:c.436A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-92609068-A-G
• chr10-92609068-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_004523.4(KIF11):​c.436A>G​(p.Lys146Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,444,900 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: KIF11 NM_004523.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.436A>G	p.Lys146Glu	missense	Exon 5 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.436A>G	p.Lys146Glu	missense	Exon 5 of 22	ENSP00000260731.3
	KIF11	ENST00000676647.1		c.229A>G	p.Lys77Glu	missense	Exon 5 of 22	ENSP00000503394.1
	KIF11	ENST00000676757.1		c.229A>G	p.Lys77Glu	missense	Exon 5 of 22	ENSP00000504289.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444900 Hom.: 0 Cov.: 29 AF XY: 0.00000557 AC XY: 4 AN XY: 718186

African (AFR) AF: 0.00 AC: 0 AN: 32790

American (AMR) AF: 0.00 AC: 0 AN: 42360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 84118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1105122

Other (OTH) AF: 0.00 AC: 0 AN: 59758

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.10	N
PhyloP100		7.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Benign	0.15	T
Sift4G	Benign	0.31	T
Polyphen		0.93	P
Vest4		0.53
MutPred		0.53		Loss of ubiquitination at K146 (P = 0.0218)
MVP		0.81
MPC		1.6
ClinPred		0.91	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.80
Mutation Taster		=48/52	disease causing

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: rs797045650; hg19: chr10-94368825;