rs786205885
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_005055.5(RAPSN):c.1084_1085insCT(p.Tyr362SerfsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y362Y) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
RAPSN
NM_005055.5 frameshift
NM_005055.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.82
Genes affected
RAPSN (HGNC:9863): (receptor associated protein of the synapse) This gene encodes a member of a family of proteins that are receptor associated proteins of the synapse. The encoded protein contains a conserved cAMP-dependent protein kinase phosphorylation site, and plays a critical role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites by linking the receptors to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin. Mutations in this gene may play a role in postsynaptic congenital myasthenic syndromes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-47438813-T-TAG is Pathogenic according to our data. Variant chr11-47438813-T-TAG is described in ClinVar as [Pathogenic]. Clinvar id is 190252.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPSN | NM_005055.5 | c.1084_1085insCT | p.Tyr362SerfsTer10 | frameshift_variant | 7/8 | ENST00000298854.7 | |
LOC124902673 | XR_007062669.1 | n.144+1049_144+1050dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPSN | ENST00000298854.7 | c.1084_1085insCT | p.Tyr362SerfsTer10 | frameshift_variant | 7/8 | 1 | NM_005055.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2016 | The c.1083_1084dupCT pathogenic variant has been reported in multiple unrelated individuals with congenital myasthenia syndromes and in each report was observed in the heterozygous state along with the N88K pathogenic variant (Richard et al., 2003; Ioos et al., 2004; Das et al., 2014). This variant causes a frameshift starting with codon Tyrosine 362, changes this amino acid to a Serine residue and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Tyr362SerfsX10. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1083_1084dupCT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1083_1084dupCT as a pathogenic variant. - |
Congenital myasthenic syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | May 14, 2021 | - - |
Congenital myasthenic syndrome 11 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at