5-155014760-C-G

Position:

• chr5-155014760-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099293.3(KIF4B):​c.901C>G​(p.Leu301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF4B NM_001099293.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117

Genes affected

KIF4B (HGNC:6322): (kinesin family member 4B) This gene is an intronless retrocopy of kinesin family member 4A. The protein encoded by this gene is a microtubule-based motor protein that plays vital roles in anaphase spindle dynamics and cytokinesis. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF4B	NM_001099293.3	c.901C>G	p.Leu301Val	missense_variant	1/1	ENST00000435029.6	NP_001092763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF4B	ENST00000435029.6	c.901C>G	p.Leu301Val	missense_variant	1/1	6	NM_001099293.3	ENSP00000387875.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2022

The c.901C>G (p.L301V) alteration is located in exon 1 (coding exon 1) of the KIF4B gene. This alteration results from a C to G substitution at nucleotide position 901, causing the leucine (L) at amino acid position 301 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.051
FATHMM_MKL	Benign	0.072	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.9	H
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.81		Loss of helix (P = 0.1299);
MVP		0.61
MPC		0.47
ClinPred		0.99	D
GERP RS		1.5
Varity_R		0.30
gMVP		0.097

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: chr5-154394320;