rs121908161

Variant summary

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

The NM_001365951.3(KIF1B):​c.2075A>T​(p.Glu692Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars). Synonymous variant affecting the same amino acid position (i.e. E692E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Failed GnomAD Quality Control

Consequence

KIF1B
NM_001365951.3 missense

Scores

11
7
1

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 9.32
Variant links:
Genes affected
KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [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
KIF1BNM_001365951.3 linkc.2075A>T p.Glu692Val missense_variant Exon 22 of 49 ENST00000676179.1 NP_001352880.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1BENST00000676179.1 linkc.2075A>T p.Glu692Val missense_variant Exon 22 of 49 NM_001365951.3 ENSP00000502065.1 O60333-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151014
Hom.:
0
Cov.:
31
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
151014
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73630
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neuroblastoma, susceptibility to, 1 Other:1
Apr 01, 2008
OMIM
Significance: risk factor
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.82
.;.;D;.;.;.;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.99
.;D;D;D;D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.35
D
MutationAssessor
Pathogenic
3.1
.;.;M;.;M;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-6.1
D;D;D;D;D;.;.
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
D;D;D;D;D;.;.
Sift4G
Uncertain
0.031
D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;.;D;.
Vest4
0.80
MutPred
0.19
.;.;Gain of methylation at K691 (P = 0.0483);.;Gain of methylation at K691 (P = 0.0483);.;.;
MVP
0.89
MPC
2.1
ClinPred
1.0
D
GERP RS
6.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.80
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs121908161; hg19: chr1-10357264; API