rs117815481
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001244008.2(KIF1A):c.4744-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,611,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001244008.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4744-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4744-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000360 AC: 88AN: 244534Hom.: 0 AF XY: 0.000360 AC XY: 48AN XY: 133396
GnomAD4 exome AF: 0.000249 AC: 363AN: 1459448Hom.: 0 Cov.: 31 AF XY: 0.000238 AC XY: 173AN XY: 725912
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 25, 2017 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | KIF1A: BP4, BP5, BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 27, 2020 | - - |
Hereditary spastic paraplegia 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
KIF1A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 06, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at