NM_004523.4:c.*1014A>T

Variant names:

• chr10-92654810-A-T
• rs4933734
• NM_004523.4:c.*1014A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004523.4(KIF11):​c.*1014A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,496 control chromosomes in the GnomAD database, including 38,731 homozygotes. 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: 𝑓 0.70 (38657 hom., cov: 32)
  • Exomes 𝑓: 0.63 (74 hom.)
• Consequence: KIF11 NM_004523.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

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.*1014A>T		3_prime_UTR	Exon 22 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.*1014A>T		3_prime_UTR	Exon 22 of 22	ENSP00000260731.3
	KIF11	ENST00000937278.1		c.*1014A>T		3_prime_UTR	Exon 22 of 22	ENSP00000607337.1
	KIF11	ENST00000676647.1		c.*1014A>T		3_prime_UTR	Exon 22 of 22	ENSP00000503394.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106377 AN: 152000 Hom.: 38602 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.635 AC: 240 AN: 378 Hom.: 74 Cov.: 0 AF XY: 0.640 AC XY: 137 AN XY: 214

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.633 AC: 233 AN: 368

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.700 AC: 106491 AN: 152118 Hom.: 38657 Cov.: 32 AF XY: 0.698 AC XY: 51908 AN XY: 74354

African (AFR) AF: 0.879 AC: 36493 AN: 41524

American (AMR) AF: 0.669 AC: 10222 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4804 AN: 5188

South Asian (SAS) AF: 0.767 AC: 3698 AN: 4822

European-Finnish (FIN) AF: 0.582 AC: 6136 AN: 10548

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40493 AN: 67966

Other (OTH) AF: 0.668 AC: 1413 AN: 2116

Alfa AF: 0.535 Hom.: 1585

Bravo AF: 0.715

Asia WGS AF: 0.806 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.85
PhyloP100		0.075
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4933734; hg19: chr10-94414567;