NM_004521.3:c.2882A>G

Variant names:

• chr10-32015539-T-C
• NM_004521.3:c.2882A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004521.3(KIF5B):​c.2882A>G​(p.Lys961Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF5B NM_004521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984219 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09060013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.2882A>G	p.Lys961Arg	missense_variant	Exon 25 of 26	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.2882A>G	p.Lys961Arg	missense_variant	Exon 25 of 25		XP_047281158.1
KIF5B	XM_047425203.1	c.2600A>G	p.Lys867Arg	missense_variant	Exon 26 of 27		XP_047281159.1
LOC107984219	XR_001747415.2	n.5354-2487T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.2882A>G	p.Lys961Arg	missense_variant	Exon 25 of 26	1	NM_004521.3	ENSP00000307078.4

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 provided Uncertain:1

Apr 17, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.12	T
Polyphen		0.42	B
Vest4		0.17
MutPred		0.18		Loss of glycosylation at K961 (P = 0.0345);
MVP		0.42
MPC		0.33
ClinPred		0.33	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.36

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: chr10-32304467;