chr10-32017339-A-T

Variant names:

• chr10-32017339-A-T
• NM_004521.3:c.2565T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004521.3(KIF5B):​c.2565T>A​(p.Asp855Glu) 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. 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: 2.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41028887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004521.3. 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
	KIF5B	NM_004521.3	MANE Select	c.2565T>A	p.Asp855Glu	missense	Exon 24 of 26	NP_004512.1	P33176

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5B	ENST00000302418.5	TSL:1 MANE Select	c.2565T>A	p.Asp855Glu	missense	Exon 24 of 26	ENSP00000307078.4	P33176
	KIF5B	ENST00000861449.1		c.2850T>A	p.Asp950Glu	missense	Exon 24 of 26	ENSP00000531508.1
	KIF5B	ENST00000861448.1		c.2562T>A	p.Asp854Glu	missense	Exon 24 of 26	ENSP00000531507.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.36
Sift	Benign	0.17	T
Sift4G	Benign	0.25	T
Polyphen		0.098	B
Vest4		0.67
MutPred		0.26		Loss of MoRF binding (P = 0.1193)
MVP		0.56
MPC		0.38
ClinPred		0.76	D
GERP RS		-1.1
Varity_R		0.26
gMVP		0.17
Mutation Taster		=67/33	polymorphism

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

hg19: chr10-32306267;