1-10232336-G-T

Variant summary

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

The NM_001365951.3(KIF1B):​c.8G>T​(p.Gly3Val) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

KIF1B
NM_001365951.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.28
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.8G>T p.Gly3Val missense_variant Exon 2 of 49 ENST00000676179.1 NP_001352880.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1BENST00000676179.1 linkc.8G>T p.Gly3Val missense_variant Exon 2 of 49 NM_001365951.3 ENSP00000502065.1 O60333-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 11, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.G3V variant (also known as c.8G>T), located in coding exon 1 of the KIF1B gene, results from a G to T substitution at nucleotide position 8. The glycine at codon 3 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
.;.;T;.;.;.;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D;D;D;D;D;D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.58
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.026
D
MutationAssessor
Uncertain
2.7
M;M;M;M;M;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-7.2
D;D;D;D;D;.;.
REVEL
Uncertain
0.58
Sift
Uncertain
0.0010
D;D;D;D;D;.;.
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D
Polyphen
0.85
P;D;B;P;.;P;.
Vest4
0.70
MutPred
0.37
Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP
0.68
MPC
2.2
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.81
gMVP
0.60

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: chr1-10292394; API