rs146628704
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006612.6(KIF1C):c.2591G>A(p.Arg864His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,574,914 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
Consequence
NM_006612.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1C | NM_006612.6 | c.2591G>A | p.Arg864His | missense_variant | 22/23 | ENST00000320785.10 | |
KIF1C | XM_005256424.3 | c.2591G>A | p.Arg864His | missense_variant | 23/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1C | ENST00000320785.10 | c.2591G>A | p.Arg864His | missense_variant | 22/23 | 1 | NM_006612.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152250Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000963 AC: 137AN: 1422664Hom.: 0 Cov.: 32 AF XY: 0.0000938 AC XY: 66AN XY: 703598
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 13, 2024 | Variant summary: KIF1C c.2591G>A (p.Arg864His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.2591G>A has been reported in the literature in an individuals affected with hereditary spastic paraplegia, without strong evidence for causality (Morais_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Spastic Ataxia 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424676). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Spastic ataxia 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 864 of the KIF1C protein (p.Arg864His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hereditary spastic paraplegia, but no second variant was identified (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424676). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at