rs1488871976
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_004984.4(KIF5A):c.572G>A(p.Arg191His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging 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. R191C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004984.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF5A | NM_004984.4 | c.572G>A | p.Arg191His | missense_variant | 7/29 | ENST00000455537.7 | |
KIF5A | NM_001354705.2 | c.305G>A | p.Arg102His | missense_variant | 4/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF5A | ENST00000455537.7 | c.572G>A | p.Arg191His | missense_variant | 7/29 | 1 | NM_004984.4 | P1 | |
KIF5A | ENST00000674619.1 | c.572G>A | p.Arg191His | missense_variant | 7/30 | ||||
KIF5A | ENST00000676457.1 | c.467G>A | p.Arg156His | missense_variant | 6/28 | ||||
KIF5A | ENST00000286452.5 | c.305G>A | p.Arg102His | missense_variant | 4/26 | 2 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251460Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135900
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460334Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726562
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 10 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at