chr17-44934241-C-A

Variant names:

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

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>T​(p.Asp293Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF18B	NM_001265577.2	c.877G>T	p.Asp293Tyr	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>T	p.Asp293Tyr	missense_variant	Exon 6 of 16	5	NM_001265577.2	ENSP00000465992.1
KIF18B	ENST00000590129.1	c.904G>T	p.Asp302Tyr	missense_variant	Exon 5 of 14	1		ENSP00000465501.1
KIF18B	ENST00000587309.5	c.877G>T	p.Asp293Tyr	missense_variant	Exon 6 of 15	5		ENSP00000465377.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457668 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724766

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109996

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	3.8	.;.;H
PhyloP100		6.0
PrimateAI	Pathogenic	0.82	D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.79
MutPred		0.62		.;.;Loss of ubiquitination at K304 (P = 0.0193);
MVP		0.88
MPC		0.92
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.89

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;