15-69416041-C-G

Variant names:

• chr15-69416041-C-G
• rs758710646
• NM_001367805.3:c.59C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367805.3(KIF23):​c.59C>G​(p.Thr20Arg) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T20M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF23 NM_001367805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

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-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06001395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	NM_001367805.3	MANE Select	c.59C>G	p.Thr20Arg	missense	Exon 2 of 24	NP_001354734.1	A0A7I2V5Y5
	KIF23	NM_138555.4		c.59C>G	p.Thr20Arg	missense	Exon 2 of 23	NP_612565.1	Q02241-1
	KIF23	NM_001367804.2		c.59C>G	p.Thr20Arg	missense	Exon 2 of 22	NP_001354733.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	ENST00000679126.1	MANE Select	c.59C>G	p.Thr20Arg	missense	Exon 2 of 24	ENSP00000504770.1	A0A7I2V5Y5
	KIF23	ENST00000260363.9	TSL:1	c.59C>G	p.Thr20Arg	missense	Exon 2 of 23	ENSP00000260363.4	Q02241-1
	KIF23	ENST00000352331.8	TSL:1	c.59C>G	p.Thr20Arg	missense	Exon 2 of 22	ENSP00000304978.6	Q02241-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.24
Sift	Benign	0.37	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.25		Gain of MoRF binding (P = 0.0134)
MVP		0.75
MPC		0.29
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.18
gMVP		0.20
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758710646; hg19: chr15-69708380;