NM_001367805.3:c.121G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001367805.3(KIF23):​c.121G>A​(p.Glu41Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

KIF23
NM_001367805.3 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.71
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 -4 ACMG points.

BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF23NM_001367805.3 linkc.121G>A p.Glu41Lys 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.121G>A p.Glu41Lys missense_variant Exon 3 of 24 NM_001367805.3 ENSP00000504770.1 A0A7I2V5Y5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250490
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135452
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460852
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726744
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.121G>A (p.E41K) alteration is located in exon 3 (coding exon 3) of the KIF23 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the glutamic acid (E) at amino acid position 41 to be replaced by a lysine (K). 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
Benign
0.30
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;T;.;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
.;D;D;D;D
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.71
D;D;D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
1.5
L;.;L;L;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.1
N;N;N;.;N
REVEL
Uncertain
0.48
Sift
Benign
0.055
T;D;T;.;T
Sift4G
Benign
0.23
T;T;T;.;T
Polyphen
1.0
D;.;D;D;.
Vest4
0.75
MutPred
0.51
Gain of methylation at E41 (P = 0.0017);Gain of methylation at E41 (P = 0.0017);Gain of methylation at E41 (P = 0.0017);Gain of methylation at E41 (P = 0.0017);Gain of methylation at E41 (P = 0.0017);
MVP
0.75
MPC
0.94
ClinPred
0.84
D
GERP RS
4.8
Varity_R
0.49
gMVP
0.46

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: rs995904166; hg19: chr15-69709761; COSMIC: COSV52979411; COSMIC: COSV52979411; API