1-10232338-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365951.3(KIF1B):​c.10G>T​(p.Ala4Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KIF1B
NM_001365951.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.04
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18626875).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1BNM_001365951.3 linkc.10G>T p.Ala4Ser 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.10G>T p.Ala4Ser missense_variant Exon 2 of 49 NM_001365951.3 ENSP00000502065.1 O60333-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.A4S variant (also known as c.10G>T), located in coding exon 1 of the KIF1B gene, results from a G to T substitution at nucleotide position 10. The alanine at codon 4 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Benign
0.94
DEOGEN2
Benign
0.13
.;.;T;.;.;.;.
Eigen
Benign
-0.052
Eigen_PC
Benign
0.19
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D;D;D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.19
T;T;T;T;T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
0.29
N;N;N;N;N;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.2
N;N;N;N;N;.;.
REVEL
Benign
0.28
Sift
Benign
0.51
T;T;T;T;T;.;.
Sift4G
Benign
0.61
T;T;T;T;T;T;T
Polyphen
0.20
B;P;B;B;.;P;.
Vest4
0.54
MutPred
0.28
Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);Gain of phosphorylation at A4 (P = 0.0203);
MVP
0.63
MPC
1.9
ClinPred
0.55
D
GERP RS
5.4
Varity_R
0.22
gMVP
0.36

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: rs371015089; hg19: chr1-10292396; API