10-92608831-T-C

Variant names:

• chr10-92608831-T-C
• rs10882088
• NM_004523.4:c.388-189T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004523.4(KIF11):​c.388-189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,244 control chromosomes in the GnomAD database, including 1,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1019 hom., cov: 32)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.594
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-92608831-T-C is Benign according to our data. Variant chr10-92608831-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4	c.388-189T>C		intron_variant	Intron 4 of 21	ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5	c.388-189T>C		intron_variant	Intron 4 of 21	1	NM_004523.4	ENSP00000260731.3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16148 AN: 152126 Hom.: 1014 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16189 AN: 152244 Hom.: 1019 Cov.: 32 AF XY: 0.108 AC XY: 8007 AN XY: 74424

African (AFR) AF: 0.144 AC: 5987 AN: 41524

American (AMR) AF: 0.155 AC: 2367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.128 AC: 662 AN: 5184

South Asian (SAS) AF: 0.165 AC: 795 AN: 4826

European-Finnish (FIN) AF: 0.0533 AC: 566 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5412 AN: 68026

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0925 Hom.: 575

Bravo AF: 0.114

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10882088; hg19: chr10-94368588;