10-32017293-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_004521.3(KIF5B):​c.2611G>A​(p.Ala871Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

KIF5B
NM_004521.3 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83
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 Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.779
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF5BNM_004521.3 linkc.2611G>A p.Ala871Thr missense_variant Exon 24 of 26 ENST00000302418.5 NP_004512.1 P33176V9HW29Q6P164
KIF5BXM_047425202.1 linkc.2611G>A p.Ala871Thr missense_variant Exon 24 of 25 XP_047281158.1
KIF5BXM_047425203.1 linkc.2329G>A p.Ala777Thr missense_variant Exon 25 of 27 XP_047281159.1
LOC107984219XR_001747415.2 linkn.5354-733C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF5BENST00000302418.5 linkc.2611G>A p.Ala871Thr missense_variant Exon 24 of 26 1 NM_004521.3 ENSP00000307078.4 P33176
KIF5BENST00000493889.1 linkn.408G>A non_coding_transcript_exon_variant Exon 5 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251010
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135664
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:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727232
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:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000761
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2611G>A (p.A871T) alteration is located in exon 24 (coding exon 24) of the KIF5B gene. This alteration results from a G to A substitution at nucleotide position 2611, causing the alanine (A) at amino acid position 871 to be replaced by a threonine (T). 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
0.47
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Uncertain
-0.083
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.44
Sift
Benign
0.28
T
Sift4G
Benign
0.58
T
Polyphen
0.96
D
Vest4
0.74
MVP
0.66
MPC
0.71
ClinPred
0.79
D
GERP RS
5.6
Varity_R
0.16
gMVP
0.31

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

LitVar

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

Other links and lift over

dbSNP: rs377196810; hg19: chr10-32306221; API