chr11-47442706-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005055.5(RAPSN):​c.640G>T​(p.Val214Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V214M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAPSN
NM_005055.5 missense

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.50

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAPSNNM_005055.5 linkc.640G>T p.Val214Leu missense_variant Exon 3 of 8 ENST00000298854.7 NP_005046.2 Q13702-1A0A0S2Z4F8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAPSNENST00000298854.7 linkc.640G>T p.Val214Leu missense_variant Exon 3 of 8 1 NM_005055.5 ENSP00000298854.2 Q13702-1
RAPSNENST00000352508.7 linkc.640G>T p.Val214Leu missense_variant Exon 3 of 6 1 ENSP00000298853.3 Q13702-2
RAPSNENST00000529341.1 linkc.640G>T p.Val214Leu missense_variant Exon 3 of 5 1 ENSP00000431732.1 E9PK11
RAPSNENST00000524487.5 linkc.532-785G>T intron_variant Intron 2 of 6 5 ENSP00000435551.2 E9PJP9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461886
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;.;.
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.3
M;M;.
PhyloP100
7.5
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.15
T;D;T
Sift4G
Benign
0.33
T;T;T
Polyphen
0.22
B;B;B
Vest4
0.78
MutPred
0.66
Loss of MoRF binding (P = 0.0986);Loss of MoRF binding (P = 0.0986);Loss of MoRF binding (P = 0.0986);
MVP
0.67
MPC
0.20
ClinPred
0.94
D
GERP RS
5.1
Varity_R
0.36
gMVP
0.53
Mutation Taster
=59/41
polymorphism

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

Other links and lift over

dbSNP: rs201124957; hg19: chr11-47464258; API