rs7111873

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005055.5(RAPSN):c.456T>C(p.Tyr152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,612,224 control chromosomes in the GnomAD database, including 397,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31209 hom., cov: 31)

Exomes 𝑓: 0.71 ( 366575 hom. )

Consequence

RAPSN
NM_005055.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-47447887-A-G is Benign according to our data. Variant chr11-47447887-A-G is described in ClinVar as [Benign]. Clinvar id is 130091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47447887-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5 linkuse as main transcript	c.456T>C	p.Tyr152=	synonymous_variant	2/8	ENST00000298854.7	NP_005046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7 linkuse as main transcript	c.456T>C	p.Tyr152=	synonymous_variant	2/8	1	NM_005055.5	ENSP00000298854	P1	Q13702-1
RAPSN	ENST00000352508.7 linkuse as main transcript	c.456T>C	p.Tyr152=	synonymous_variant	2/6	1		ENSP00000298853		Q13702-2
RAPSN	ENST00000529341.1 linkuse as main transcript	c.456T>C	p.Tyr152=	synonymous_variant	2/5	1		ENSP00000431732
RAPSN	ENST00000524487.5 linkuse as main transcript	c.456T>C	p.Tyr152=	synonymous_variant	2/7	5		ENSP00000435551

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95043

AN:

151872

Hom.:

31192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.721

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.680

AC:

168439

AN:

247528

Hom.:

58478

AF XY:

0.694

AC XY:

93159

AN XY:

134156

show subpopulations

Gnomad AFR exome

AF:

0.414

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.720

Gnomad EAS exome

AF:

0.646

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.723

Gnomad OTH exome

AF:

0.722

GnomAD4 exome

AF:

0.706

AC:

1030270

AN:

1460234

Hom.:

366575

Cov.:

AF XY:

0.709

AC XY:

515005

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.625

Gnomad4 ASJ exome

AF:

0.720

Gnomad4 EAS exome

AF:

0.601

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.719

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.626

AC:

95101

AN:

151990

Hom.:

31209

Cov.:

AF XY:

0.624

AC XY:

46332

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.670

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.660

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.721

Gnomad4 OTH

AF:

0.689

Alfa

AF:

0.699

Hom.:

22867

Bravo

AF:

0.618

Asia WGS

AF:

0.720

AC:

2509

AN:

3478

EpiCase

AF:

0.736

EpiControl

AF:

0.737

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 07, 2015	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	-	- -

Congenital myasthenic syndrome 11

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital myasthenic syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Fetal akinesia deformation sequence 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.016

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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