rs201825284
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS1_Supporting
The NM_001244008.2(KIF1A):c.4781C>T(p.Ser1594Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,610,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1594S) has been classified as Likely benign.
Frequency
Consequence
NM_001244008.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.4781C>T | p.Ser1594Leu | missense_variant | 45/49 | ENST00000498729.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.4781C>T | p.Ser1594Leu | missense_variant | 45/49 | 5 | NM_001244008.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000466 AC: 71AN: 152212Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000255 AC: 62AN: 242990Hom.: 1 AF XY: 0.000241 AC XY: 32AN XY: 132516
GnomAD4 exome AF: 0.000145 AC: 212AN: 1458646Hom.: 1 Cov.: 31 AF XY: 0.000138 AC XY: 100AN XY: 725396
GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152330Hom.: 1 Cov.: 33 AF XY: 0.000577 AC XY: 43AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 29, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2021 | The c.4478C>T (p.S1493L) alteration is located in exon 43 (coding exon 42) of the KIF1A gene. This alteration results from a C to T substitution at nucleotide position 4478, causing the serine (S) at amino acid position 1493 to be replaced by a leucine (L). 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 | Mar 01, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2022 | Reported in a patient in the published literature with caudal regression syndrome who had another KIF1A variant on the opposite allele (in trans); however, the patient also had variants in two other genes that may have been responsible for the phenotype (Porsch et al., 2016); Identified heterozygous in a patient with congenital spastic paraplegia, intellectual disability, epilepsy, microcephaly, and brain abnormalities in published literature; however, familial segregation information was not available (Nicita et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.(S1594L); This variant is associated with the following publications: (PMID: 28007035, 32737135) - |
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