17-44934241-C-G

Variant names:

• chr17-44934241-C-G
• rs118010375
• NM_001265577.2:c.877G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001265577.2(KIF18B):​c.877G>C​(p.Asp293His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D293N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIF18B NM_001265577.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

KIF18B (HGNC:27102): (kinesin family member 18B) Enables cytoskeletal motor activity and kinesin binding activity. Involved in microtubule depolymerization; mitotic cell cycle; and regulation of cell division. Located in cytosol; microtubule; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF18B	NM_001265577.2	c.877G>C	p.Asp293His	missense_variant	Exon 6 of 16	ENST00000593135.6	NP_001252506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF18B	ENST00000593135.6	c.877G>C	p.Asp293His	missense_variant	Exon 6 of 16	5	NM_001265577.2	ENSP00000465992.1
KIF18B	ENST00000590129.1	c.904G>C	p.Asp302His	missense_variant	Exon 5 of 14	1		ENSP00000465501.1
KIF18B	ENST00000587309.5	c.877G>C	p.Asp293His	missense_variant	Exon 6 of 15	5		ENSP00000465377.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Uncertain	2.8	.;.;M
PhyloP100		6.0
PrimateAI	Pathogenic	0.83	D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.73
MutPred		0.60		.;.;Loss of ubiquitination at K304 (P = 0.0228);
MVP		0.91
MPC		0.90
ClinPred		0.97	D
GERP RS		5.8
gMVP		0.81

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

Other links and lift over

dbSNP: rs118010375; hg19: chr17-43011609;