15-69416058-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367805.3(KIF23):​c.76G>A​(p.Val26Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,572,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

KIF23
NM_001367805.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14
Variant links:
Genes affected
KIF23 (HGNC:6392): (kinesin family member 23) The protein encoded by this gene is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2615913).
BS2
High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF23NM_001367805.3 linkc.76G>A p.Val26Ile missense_variant Exon 2 of 24 ENST00000679126.1 NP_001354734.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF23ENST00000679126.1 linkc.76G>A p.Val26Ile missense_variant Exon 2 of 24 NM_001367805.3 ENSP00000504770.1 A0A7I2V5Y5

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000139
AC:
30
AN:
215310
Hom.:
0
AF XY:
0.000136
AC XY:
16
AN XY:
117848
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000134
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000241
Gnomad OTH exome
AF:
0.000402
GnomAD4 exome
AF:
0.000263
AC:
374
AN:
1419942
Hom.:
0
Cov.:
28
AF XY:
0.000238
AC XY:
168
AN XY:
705996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000153
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.000328
Gnomad4 OTH exome
AF:
0.000136
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152344
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000223
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000132
AC:
16

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Nov 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 26 of the KIF23 protein (p.Val26Ile). This variant is present in population databases (rs139012996, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with KIF23-related conditions. ClinVar contains an entry for this variant (Variation ID: 2175905). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KIF23 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T;T;.;T;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
.;D;D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.3
L;.;L;L;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.69
N;N;N;.;N
REVEL
Uncertain
0.35
Sift
Benign
0.049
D;D;D;.;D
Sift4G
Uncertain
0.056
T;T;T;.;T
Polyphen
1.0
D;.;D;D;.
Vest4
0.42
MVP
0.67
MPC
0.30
ClinPred
0.18
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139012996; hg19: chr15-69708397; API