Variant chr15-69417390-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_001367805.3(KIF23):c.89G>T(p.Cys30Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIF23
NM_001367805.3 missense

Scores

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]

KIF23 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF23. . Gene score misZ 2.0848 (greater than the threshold 3.09). Trascript score misZ 3.2738 (greater than threshold 3.09). GenCC has associacion of gene with congenital dyserythropoietic anemia type 3.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF23	NM_001367805.3 linkuse as main transcript	c.89G>T	p.Cys30Phe	missense_variant	3/24	ENST00000679126.1	NP_001354734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF23	ENST00000679126.1 linkuse as main transcript	c.89G>T	p.Cys30Phe	missense_variant	3/24		NM_001367805.3	ENSP00000504770	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455978

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724214

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.89G>T (p.C30F) alteration is located in exon 3 (coding exon 3) of the KIF23 gene. This alteration results from a G to T substitution at nucleotide position 89, causing the cysteine (C) at amino acid position 30 to be replaced by a phenylalanine (F). 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;.;T;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.91

D;D;D;D;D

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

3.6

H;.;H;H;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-9.2

D;D;D;.;D

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;.;D

Polyphen

1.0

D;.;D;D;.

Vest4

0.85

MutPred

0.50

Loss of catalytic residue at V32 (P = 0.0969);Loss of catalytic residue at V32 (P = 0.0969);Loss of catalytic residue at V32 (P = 0.0969);Loss of catalytic residue at V32 (P = 0.0969);Loss of catalytic residue at V32 (P = 0.0969);

MVP

0.84

MPC

1.1

ClinPred

1.0

GERP RS

4.8

Varity_R

0.99

gMVP

0.72

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over