rs756912340
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001244008.2(KIF1A):c.5087G>A(p.Arg1696His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,612,412 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1696C) has been classified as Likely benign.
Frequency
Consequence
NM_001244008.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.5087G>A | p.Arg1696His | missense_variant | 47/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.5087G>A | p.Arg1696His | missense_variant | 47/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000403 AC: 10AN: 248110Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134800
GnomAD4 exome AF: 0.0000794 AC: 116AN: 1460242Hom.: 0 Cov.: 31 AF XY: 0.0000909 AC XY: 66AN XY: 726392
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Oct 17, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 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) - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2019 | The p.R1595H variant (also known as c.4784G>A), located in coding exon 44 of the KIF1A gene, results from a G to A substitution at nucleotide position 4784. The arginine at codon 1595 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Neuropathy, hereditary sensory and autonomic, type 2A;C3280168: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 | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at