rs772124743

Variant names:

• chr10-32015558-C-A
• NM_004521.3:c.2863G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-32015558-C-A
• chr10-32015558-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004521.3(KIF5B):​c.2863G>T​(p.Val955Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. V955M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: KIF5B NM_004521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037075907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.2863G>T	p.Val955Leu	missense_variant	Exon 25 of 26	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.2863G>T	p.Val955Leu	missense_variant	Exon 25 of 25		XP_047281158.1
KIF5B	XM_047425203.1	c.2581G>T	p.Val861Leu	missense_variant	Exon 26 of 27		XP_047281159.1
LOC107984219	XR_001747415.2	n.5354-2468C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.2863G>T	p.Val955Leu	missense_variant	Exon 25 of 26	1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460830 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.42	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.10
Sift	Benign	0.57	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.22		Loss of catalytic residue at V955 (P = 0.0831);
MVP		0.22
MPC		0.39
ClinPred		0.14	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-32304486;