2-240745884-TAGG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_001244008.2(KIF1A):βc.3225_3227delβ(p.Leu1076del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000118 in 1,608,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 33)
Exomes π: 0.000012 ( 0 hom. )
Consequence
KIF1A
NM_001244008.2 inframe_deletion
NM_001244008.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.76
Genes affected
KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001244008.2. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.3225_3227del | p.Leu1076del | inframe_deletion | 31/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.3225_3227del | p.Leu1076del | inframe_deletion | 31/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000124 AC: 3AN: 242342Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132026
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1455940Hom.: 0 AF XY: 0.0000138 AC XY: 10AN XY: 723392
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 22, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 15, 2022 | Variant summary: KIF1A c.2922_2924delCCT (p.Leu975del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 242342 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2922_2924delCCT in individuals affected with NESCAV Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 24, 2017 | - - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This variant, c.2922_2924del, results in the deletion of 1 amino acid(s) of the KIF1A protein (p.Leu975del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KIF1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 435627). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at