10-92593161-A-G

Position:

• chr10-92593161-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004523.4(KIF11):​c.-215A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 531,838 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (358 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (77 hom.)
• Consequence: KIF11 NM_004523.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-92593161-A-G is Benign according to our data. Variant chr10-92593161-A-G is described in ClinVar as [Benign]. Clinvar id is 1279872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF11	NM_004523.4	c.-215A>G		5_prime_UTR_premature_start_codon_gain_variant	1/22	ENST00000260731.5	NP_004514.2
KIF11	NM_004523.4	c.-215A>G		5_prime_UTR_variant	1/22	ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731	c.-215A>G		5_prime_UTR_premature_start_codon_gain_variant	1/22	1	NM_004523.4	ENSP00000260731.3
KIF11	ENST00000260731	c.-215A>G		5_prime_UTR_variant	1/22	1	NM_004523.4	ENSP00000260731.3

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5347 AN: 152196 Hom.: 357 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.00419 AC: 1590 AN: 379524 Hom.: 77 AF XY: 0.00371 AC XY: 742 AN XY: 200232

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000502

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0352 AC: 5362 AN: 152314 Hom.: 358 Cov.: 33 AF XY: 0.0334 AC XY: 2490 AN XY: 74490

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0240 Hom.: 22

Bravo AF: 0.0395

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113197692; hg19: chr10-94352918;