rs368005947
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001244008.2(KIF1A):c.4529C>T(p.Pro1510Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,563,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1510R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001244008.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4529C>T | p.Pro1510Leu | missense_variant | 43/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4529C>T | p.Pro1510Leu | missense_variant | 43/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000453 AC: 8AN: 176508Hom.: 0 AF XY: 0.0000421 AC XY: 4AN XY: 95120
GnomAD4 exome AF: 0.0000312 AC: 44AN: 1411778Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 19AN XY: 697560
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 29, 2018 | The p.P1409L variant (also known as c.4226C>T), located in coding exon 40 of the KIF1A gene, results from a C to T substitution at nucleotide position 4226. The proline at codon 1409 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved through mammals but not in all 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary spastic paraplegia 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
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 | Dec 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at