11-47448793-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005055.5(RAPSN):c.172C>T(p.Arg58Cys) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 1,611,616 control chromosomes in the GnomAD database, including 10,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R58H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005055.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPSN | NM_005055.5 | c.172C>T | p.Arg58Cys | missense_variant | 1/8 | ENST00000298854.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPSN | ENST00000298854.7 | c.172C>T | p.Arg58Cys | missense_variant | 1/8 | 1 | NM_005055.5 | P1 | |
RAPSN | ENST00000352508.7 | c.172C>T | p.Arg58Cys | missense_variant | 1/6 | 1 | |||
RAPSN | ENST00000529341.1 | c.172C>T | p.Arg58Cys | missense_variant | 1/5 | 1 | |||
RAPSN | ENST00000524487.5 | c.172C>T | p.Arg58Cys | missense_variant | 1/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0884 AC: 13458AN: 152162Hom.: 876 Cov.: 32
GnomAD3 exomes AF: 0.104 AC: 25909AN: 249460Hom.: 1749 AF XY: 0.107 AC XY: 14413AN XY: 135058
GnomAD4 exome AF: 0.107 AC: 156705AN: 1459336Hom.: 9537 Cov.: 32 AF XY: 0.108 AC XY: 78523AN XY: 726112
GnomAD4 genome AF: 0.0884 AC: 13454AN: 152280Hom.: 876 Cov.: 32 AF XY: 0.0950 AC XY: 7077AN XY: 74470
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 28, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Congenital myasthenic syndrome 11 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Fetal akinesia deformation sequence 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Fetal akinesia deformation sequence 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Congenital myasthenic syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at