rs45603036

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005055.5(RAPSN):c.855G>A(p.Gln285Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,609,464 control chromosomes in the GnomAD database, including 13,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 972 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12957 hom. )

Consequence

RAPSN
NM_005055.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.92

Variant links:

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]

RAPSN links:

LOC124902673 (HGNC:):

LOC124902673 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-47441668-C-T is Benign according to our data. Variant chr11-47441668-C-T is described in ClinVar as [Benign]. Clinvar id is 130092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47441668-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPSN	NM_005055.5 link	c.855G>A	p.Gln285Gln	synonymous_variant	Exon 5 of 8	ENST00000298854.7	NP_005046.2	Q13702-1A0A0S2Z4F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7 link	c.855G>A	p.Gln285Gln	synonymous_variant	Exon 5 of 8	1	NM_005055.5	ENSP00000298854.2		Q13702-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16025

AN:

152132

Hom.:

972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0881

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.105

AC:

25850

AN:

245276

Hom.:

1604

AF XY:

0.107

AC XY:

14208

AN XY:

133232

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.0568

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0356

Gnomad SAS exome

AF:

0.0602

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.129

AC:

187755

AN:

1457214

Hom.:

12957

Cov.:

AF XY:

0.127

AC XY:

92385

AN XY:

725022

show subpopulations

Gnomad4 AFR exome

AF:

0.0617

Gnomad4 AMR exome

AF:

0.0606

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.0270

Gnomad4 SAS exome

AF:

0.0635

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.105

AC:

16027

AN:

152250

Hom.:

972

Cov.:

AF XY:

0.103

AC XY:

7655

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0639

Gnomad4 AMR

AF:

0.0879

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0379

Gnomad4 SAS

AF:

0.0542

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.126

Hom.:

617

Bravo

AF:

0.102

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.145

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 13, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Congenital myasthenic syndrome 11

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 11;C4760576:Fetal akinesia deformation sequence 2

Benign:1

Mar 28, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia deformation sequence 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia deformation sequence 2

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.2

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over