chr11-47448127-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005055.5(RAPSN):c.216G>A(p.Thr72Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,612,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
RAPSN
NM_005055.5 synonymous
NM_005055.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.96
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 11-47448127-C-T is Benign according to our data. Variant chr11-47448127-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 448158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.96 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RAPSN | NM_005055.5 | c.216G>A | p.Thr72Thr | synonymous_variant | Exon 2 of 8 | ENST00000298854.7 | NP_005046.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RAPSN | ENST00000298854.7 | c.216G>A | p.Thr72Thr | synonymous_variant | Exon 2 of 8 | 1 | NM_005055.5 | ENSP00000298854.2 | ||
| RAPSN | ENST00000352508.7 | c.216G>A | p.Thr72Thr | synonymous_variant | Exon 2 of 6 | 1 | ENSP00000298853.3 | |||
| RAPSN | ENST00000529341.1 | c.216G>A | p.Thr72Thr | synonymous_variant | Exon 2 of 5 | 1 | ENSP00000431732.1 | |||
| RAPSN | ENST00000524487.5 | c.216G>A | p.Thr72Thr | synonymous_variant | Exon 2 of 7 | 5 | ENSP00000435551.2 |
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000157 AC: 39AN: 248772Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 134720
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GnomAD4 exome AF: 0.0000767 AC: 112AN: 1460632Hom.: 0 Cov.: 36 AF XY: 0.0000702 AC XY: 51AN XY: 726642
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GnomAD4 genome 0.0000723 AC: 11AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74424
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Jun 30, 2017
Athena Diagnostics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
RAPSN-related disorder Benign:1
Oct 21, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 Benign:1
Apr 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at