11-47438011-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_005055.5(RAPSN):c.1203C>T(p.Asn401Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,550,234 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

RAPSN
NM_005055.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 2.53

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

fetal akinesia deformation sequence 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
neuromuscular disease
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
congenital myasthenic syndrome 11
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp
fetal akinesia deformation sequence 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RAPSN links:

LOC124902673 (HGNC:):

LOC124902673 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-47438011-G-A is Benign according to our data. Variant chr11-47438011-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 285425.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BP7

Synonymous conserved (PhyloP=2.53 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPSN	NM_005055.5 link	c.1203C>T	p.Asn401Asn	synonymous_variant	Exon 8 of 8	ENST00000298854.7	NP_005046.2	Q13702-1A0A0S2Z4F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAPSN	ENST00000298854.7 link	c.1203C>T	p.Asn401Asn	synonymous_variant	Exon 8 of 8	1	NM_005055.5	ENSP00000298854.2	Q13702-1
RAPSN	ENST00000352508.7 link	c.1026C>T	p.Asn342Asn	synonymous_variant	Exon 6 of 6	1		ENSP00000298853.3	Q13702-2
RAPSN	ENST00000524487.5 link	c.1044C>T	p.Asn348Asn	synonymous_variant	Exon 7 of 7	5		ENSP00000435551.2	E9PJP9
RAPSN	ENST00000528356.1 link	n.158C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000102

AC:

AN:

156248

AF XY:

0.0000973

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000180

AC:

251

AN:

1398036

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

113

AN XY:

689504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31546

American (AMR)

AF:

0.0000280

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35740

South Asian (SAS)

AF:

0.00

AC:

AN:

79164

European-Finnish (FIN)

AF:

0.000345

AC:

AN:

49258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4608

European-Non Finnish (NFE)

AF:

0.000209

AC:

226

AN:

1078958

Other (OTH)

AF:

0.000121

AC:

AN:

57878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000177

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000213

Hom.:

Bravo

AF:

0.000159

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RAPSN: BP4, BP7 -

Jan 15, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RAPSN-related disorder

Benign:1

Jul 03, 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

Aug 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Likely 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

-0.56

CADD

Benign

9.2

(source)

DANN

Benign

0.86

PhyloP100

2.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-47438011-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over