SPAST p.Ser458Ser
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2
Uncertain significance
The NM_014946.4(SPAST):c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Consequence
SPAST
NM_014946.4 intron
NM_014946.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.66
Publications
0 publications found
Genes affected
SPAST (HGNC:11233): (spastin) This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The use of alternative translational initiation sites in this gene results in a single transcript variant that can produce isoforms that differ in the length of their N-terminus and which thereby differ in the efficiency of their export from the nucleus to the cytoplasm. In addition, alternative splicing results in multiple transcript variants that encode isoforms that differ in other protein regions as well. One isoform of this gene has been shown to be a microtubule-severing enzyme that regulates microtubule abundance, mobility, and plus-end distribution. Mutations in this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, May 2018]
SPAST Gene-Disease associations (from GenCC):
- hereditary spastic paraplegia 4Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Illumina, PanelApp Australia
- neurodevelopmental disorderInheritance: AD Classification: STRONG Submitted by: G2P
- SPAST-related motor disorderInheritance: AR Classification: STRONG Submitted by: Ambry Genetics
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new If you want to explore the variant's impact on the transcript NM_014946.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_014946.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SPAST | TSL:1 MANE Select | c. | exon_region | Exon 11 of 17 | ENSP00000320885.3 | Q9UBP0-1 | |||
| SPAST | TSL:1 | c. | exon_region | Exon 11 of 17 | ENSP00000482496.2 | A0A2U3TZR0 | |||
| SPAST | c. | exon_region | Exon 12 of 18 | ENSP00000519019.1 | A0AAQ5BGQ0 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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