rs132630294
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000533.5(PLP1):c.509C>T(p.Ser170Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S170P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000533.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLP1 | NM_000533.5 | c.509C>T | p.Ser170Phe | missense_variant | 4/7 | ENST00000621218.5 | NP_000524.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLP1 | ENST00000621218.5 | c.509C>T | p.Ser170Phe | missense_variant | 4/7 | 1 | NM_000533.5 | ENSP00000484450.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 17, 1998 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2021 | Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24077912, 27535533, 9489796) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at