10-32021114-C-A

Variant summary

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

The NM_004521.3(KIF5B):​c.2112G>T​(p.Gln704His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIF5B
NM_004521.3 missense

Scores

6
12
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
KIF5BNM_004521.3 linkc.2112G>T p.Gln704His missense_variant Exon 19 of 26 ENST00000302418.5 NP_004512.1 P33176V9HW29Q6P164
KIF5BXM_047425202.1 linkc.2112G>T p.Gln704His missense_variant Exon 19 of 25 XP_047281158.1
KIF5BXM_047425203.1 linkc.1830G>T p.Gln610His missense_variant Exon 20 of 27 XP_047281159.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF5BENST00000302418.5 linkc.2112G>T p.Gln704His missense_variant Exon 19 of 26 1 NM_004521.3 ENSP00000307078.4 P33176
KIF5BENST00000493889.1 linkn.-20G>T upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251220
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461414
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727030
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2112G>T (p.Q704H) alteration is located in exon 19 (coding exon 19) of the KIF5B gene. This alteration results from a G to T substitution at nucleotide position 2112, causing the glutamine (Q) at amino acid position 704 to be replaced by a histidine (H). 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
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Uncertain
0.49
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.3
D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.99
D
Vest4
0.60
MutPred
0.067
Loss of MoRF binding (P = 0.1297);
MVP
0.71
MPC
1.0
ClinPred
0.99
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.70
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1467010566; hg19: chr10-32310042; API