rs201474903
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001365951.3(KIF1B):c.1364C>A(p.Thr455Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T455T) has been classified as Benign.
Frequency
Consequence
NM_001365951.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF1B | NM_001365951.3 | c.1364C>A | p.Thr455Lys | missense_variant | 15/49 | ENST00000676179.1 | NP_001352880.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF1B | ENST00000676179.1 | c.1364C>A | p.Thr455Lys | missense_variant | 15/49 | NM_001365951.3 | ENSP00000502065 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251294Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135792
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461862Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 727230
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2022 | The p.T409K variant (also known as c.1226C>A), located in coding exon 12 of the KIF1B gene, results from a C to A substitution at nucleotide position 1226. The threonine at codon 409 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 18, 2023 | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 409 of the KIF1B protein (p.Thr409Lys). This variant is present in population databases (rs201474903, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with KIF1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1754281). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at