chr15-69416045-C-A

Position:

• chr15-69416045-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001367805.3(KIF23):​c.63C>A​(p.Asn21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF23 NM_001367805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.420

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.055503786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF23	NM_001367805.3	c.63C>A	p.Asn21Lys	missense_variant	2/24	ENST00000679126.1	NP_001354734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF23	ENST00000679126.1	c.63C>A	p.Asn21Lys	missense_variant	2/24		NM_001367805.3	ENSP00000504770	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 29, 2022

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with KIF23-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 21 of the KIF23 protein (p.Asn21Lys). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.013	T;T;.;T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.83	.;T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.056	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;.;L;L;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.80	N;N;N;.;N
REVEL	Benign	0.074
Sift	Benign	0.87	T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;.;T
Polyphen		0.0030	B;.;B;B;.
Vest4		0.13
MutPred		0.32		Gain of methylation at N21 (P = 0.0117);Gain of methylation at N21 (P = 0.0117);Gain of methylation at N21 (P = 0.0117);Gain of methylation at N21 (P = 0.0117);Gain of methylation at N21 (P = 0.0117);
MVP		0.45
MPC		0.29
ClinPred		0.079	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.070

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.

Other links and lift over

hg19: chr15-69708384;