chr15-69417401-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001367805.3(KIF23):​c.100C>A​(p.Pro34Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,610,982 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00074 ( 0 hom. )

Consequence

KIF23
NM_001367805.3 missense

Scores

11
7
1

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 7.68
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 -5 ACMG points.

BP6
Variant 15-69417401-C-A is Benign according to our data. Variant chr15-69417401-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1533388.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS2
High AC in GnomAd4 at 87 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF23NM_001367805.3 linkc.100C>A p.Pro34Thr missense_variant Exon 3 of 24 ENST00000679126.1 NP_001354734.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF23ENST00000679126.1 linkc.100C>A p.Pro34Thr missense_variant Exon 3 of 24 NM_001367805.3 ENSP00000504770.1 A0A7I2V5Y5

Frequencies

GnomAD3 genomes
AF:
0.000572
AC:
87
AN:
152142
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000970
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000579
AC:
144
AN:
248588
Hom.:
0
AF XY:
0.000580
AC XY:
78
AN XY:
134468
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.000327
Gnomad ASJ exome
AF:
0.000499
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00107
Gnomad OTH exome
AF:
0.000662
GnomAD4 exome
AF:
0.000736
AC:
1074
AN:
1458722
Hom.:
0
Cov.:
32
AF XY:
0.000736
AC XY:
534
AN XY:
725698
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.000340
Gnomad4 ASJ exome
AF:
0.000307
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000701
Gnomad4 FIN exome
AF:
0.0000563
Gnomad4 NFE exome
AF:
0.000881
Gnomad4 OTH exome
AF:
0.000863
GnomAD4 genome
AF:
0.000571
AC:
87
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.000537
AC XY:
40
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000970
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000960
Hom.:
0
Bravo
AF:
0.000654
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.000626
AC:
76

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Jan 12, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Apr 09, 2021
Mayo Clinic Laboratories, Mayo Clinic
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.100C>A (p.P34T) alteration is located in exon 3 (coding exon 3) of the KIF23 gene. This alteration results from a C to A substitution at nucleotide position 100, causing the proline (P) at amino acid position 34 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.44
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.82
D;D;.;D;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
.;D;D;D;D
M_CAP
Pathogenic
0.29
D
MetaRNN
Uncertain
0.60
D;D;D;D;D
MetaSVM
Pathogenic
0.96
D
MutationAssessor
Pathogenic
3.8
H;.;H;H;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-6.3
D;D;D;.;D
REVEL
Pathogenic
0.95
Sift
Uncertain
0.0020
D;D;D;.;D
Sift4G
Uncertain
0.0060
D;D;D;.;D
Polyphen
1.0
D;.;D;D;.
Vest4
0.94
MVP
0.96
MPC
0.95
ClinPred
0.31
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.73

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: rs148511930; hg19: chr15-69709740; API