11-47442684-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005055.5(RAPSN):c.662G>A(p.Arg221His) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. R221C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005055.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPSN | NM_005055.5 | c.662G>A | p.Arg221His | missense_variant | 3/8 | ENST00000298854.7 | |
LOC124902673 | XR_007062669.1 | n.145-4643C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPSN | ENST00000298854.7 | c.662G>A | p.Arg221His | missense_variant | 3/8 | 1 | NM_005055.5 | P1 | |
RAPSN | ENST00000352508.7 | c.662G>A | p.Arg221His | missense_variant | 3/6 | 1 | |||
RAPSN | ENST00000529341.1 | c.662G>A | p.Arg221His | missense_variant | 3/5 | 1 | |||
RAPSN | ENST00000524487.5 | c.532-763G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250878Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135668
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461872Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727240
GnomAD4 genome Cov.: 33
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 | May 05, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 221 of the RAPSN protein (p.Arg221His). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RAPSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 476124). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Congenital myasthenic syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 26, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at