rs199804623
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BS1_Supporting
The NM_001244008.2(KIF1A):c.5168C>T(p.Ala1723Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,612,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A1723T) has been classified as Likely benign.
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.5168C>T | p.Ala1723Val | missense_variant | 47/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.5168C>T | p.Ala1723Val | missense_variant | 47/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000278 AC: 69AN: 248364Hom.: 0 AF XY: 0.000230 AC XY: 31AN XY: 134928
GnomAD4 exome AF: 0.000455 AC: 665AN: 1460154Hom.: 0 Cov.: 31 AF XY: 0.000469 AC XY: 341AN XY: 726334
GnomAD4 genome AF: 0.000263 AC: 40AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:5Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 15, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 12, 2018 | The KIF1A c.4865C>T; p.Ala1622Val variant (rs199804623), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.04% (identified on 52 out of 126,068 chromosomes). The alanine at position 1622 is weakly conserved, considering 13 species, and computational analyses of the effects of the p.Ala1622Val variant on protein structure and function make conflicting predictions (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ala1622Val variant cannot be determined with certainty. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 07, 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; This variant is associated with the following publications: (PMID: 26125038, 21820098, 21376300) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 30, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | KIF1A: PP2 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The c.5168C>T (p.A1723V) alteration is located in exon 47 (coding exon 46) of the KIF1A gene. This alteration results from a C to T substitution at nucleotide position 5168, causing the alanine (A) at amino acid position 1723 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 08, 2021 | - - |
Intellectual disability, autosomal dominant 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
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 | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at