rs748016594

Variant names:

• chr15-69426090-T-A
• rs748016594
• NM_001367805.3:c.797T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-69426090-T-A
• chr15-69426090-T-C
• chr15-69426090-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_001367805.3(KIF23):​c.797T>A​(p.Leu266His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF23 NM_001367805.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.82

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855
• PP5: Variant 15-69426090-T-A is Pathogenic according to our data. Variant chr15-69426090-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 402143.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-69426090-T-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF23	NM_001367805.3	c.797T>A	p.Leu266His	missense_variant	Exon 9 of 24	ENST00000679126.1	NP_001354734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF23	ENST00000679126.1	c.797T>A	p.Leu266His	missense_variant	Exon 9 of 24		NM_001367805.3	ENSP00000504770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly Pathogenic:1

-

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

KIF23 is predicted to interact with several genes previously associated with microcephaly -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;D;.;D;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Pathogenic	3.1	M;.;M;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.9	D;D;D;.;.
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;.;.
Polyphen		1.0	D;.;D;D;.
Vest4		0.88
MutPred		0.60		Loss of stability (P = 0.0036);Loss of stability (P = 0.0036);Loss of stability (P = 0.0036);Loss of stability (P = 0.0036);.;
MVP		0.95
MPC		1.0
ClinPred		1.0	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.91
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs748016594; hg19: chr15-69718429;