rs1555143594
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005055.5(RAPSN):c.175T>C(p.Tyr59His) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y59C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005055.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPSN | NM_005055.5 | c.175T>C | p.Tyr59His | missense_variant | 1/8 | ENST00000298854.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPSN | ENST00000298854.7 | c.175T>C | p.Tyr59His | missense_variant | 1/8 | 1 | NM_005055.5 | P1 | |
RAPSN | ENST00000352508.7 | c.175T>C | p.Tyr59His | missense_variant | 1/6 | 1 | |||
RAPSN | ENST00000529341.1 | c.175T>C | p.Tyr59His | missense_variant | 1/5 | 1 | |||
RAPSN | ENST00000524487.5 | c.175T>C | p.Tyr59His | missense_variant | 1/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2016 | This sequence change replaces tyrosine with histidine at codon 59 of the RAPSN protein (p.Tyr59His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RAPSN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at