Genetic Variant RAPSN:p.Asn401Lys (chr11-47438011-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005055.5(RAPSN):c.1203C>A(p.Asn401Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N401N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAPSN
NM_005055.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11695793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPSN	NM_005055.5 link	c.1203C>A	p.Asn401Lys	missense_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>A	p.Asn401Lys	missense_variant	Exon 8 of 8	1	NM_005055.5	ENSP00000298854.2	Q13702-1
RAPSN	ENST00000352508.7 link	c.1026C>A	p.Asn342Lys	missense_variant	Exon 6 of 6	1		ENSP00000298853.3	Q13702-2
RAPSN	ENST00000524487.5 link	c.1044C>A	p.Asn348Lys	missense_variant	Exon 7 of 7	5		ENSP00000435551.2	E9PJP9
RAPSN	ENST00000528356.1 link	n.158C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1398036

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689504

African (AFR)

AF:

0.00

AC:

AN:

31546

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

49258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4608

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078958

Other (OTH)

AF:

0.00

AC:

AN:

57878

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;.;.

PhyloP100

2.5

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.87

N;N;.

REVEL

Benign

0.045

Sift

Benign

0.35

T;T;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.15

MutPred

0.42

Gain of methylation at N401 (P = 0.0016);.;.;

MVP

0.44

MPC

0.20

ClinPred

0.55

GERP RS

2.4

Varity_R

0.18

gMVP

0.41

Mutation Taster

=70/30

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over