rs45603036

Variant names:

• chr11-47441668-C-T
• rs45603036
• NM_005055.5:c.855G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.92
• Publications: 11 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• neuromuscular disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• congenital myasthenic syndrome 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), 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

LOC124902673 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 130092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005055.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPSN	NM_005055.5	MANE Select	c.855G>A	p.Gln285Gln	synonymous	Exon 5 of 8	NP_005046.2
	RAPSN	NM_001440490.1		c.855G>A	p.Gln285Gln	synonymous	Exon 5 of 8	NP_001427419.1
	RAPSN	NM_001440491.1		c.855G>A	p.Gln285Gln	synonymous	Exon 5 of 8	NP_001427420.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPSN	ENST00000298854.7	TSL:1 MANE Select	c.855G>A	p.Gln285Gln	synonymous	Exon 5 of 8	ENSP00000298854.2	Q13702-1
	RAPSN	ENST00000352508.7	TSL:1	c.789+155G>A		intron	N/A	ENSP00000298853.3	Q13702-2
	RAPSN	ENST00000529341.1	TSL:1	c.789+155G>A		intron	N/A	ENSP00000431732.1	E9PK11

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16025 AN: 152132 Hom.: 972 Cov.: 32

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

GnomAD2 exomes AF: 0.105 AC: 25850 AN: 245276 AF XY: 0.107

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 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.: 33 AF XY: 0.127 AC XY: 92385 AN XY: 725022

African (AFR) AF: 0.0617 AC: 2066 AN: 33468

American (AMR) AF: 0.0606 AC: 2703 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3789 AN: 26084

East Asian (EAS) AF: 0.0270 AC: 1072 AN: 39678

South Asian (SAS) AF: 0.0635 AC: 5471 AN: 86094

European-Finnish (FIN) AF: 0.135 AC: 6673 AN: 49478

Middle Eastern (MID) AF: 0.131 AC: 757 AN: 5766

European-Non Finnish (NFE) AF: 0.142 AC: 157898 AN: 1111690

Other (OTH) AF: 0.121 AC: 7326 AN: 60328

GnomAD4 genome AF: 0.105 AC: 16027 AN: 152250 Hom.: 972 Cov.: 32 AF XY: 0.103 AC XY: 7655 AN XY: 74436

African (AFR) AF: 0.0639 AC: 2654 AN: 41556

American (AMR) AF: 0.0879 AC: 1345 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3472

East Asian (EAS) AF: 0.0379 AC: 196 AN: 5178

South Asian (SAS) AF: 0.0542 AC: 262 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9422 AN: 67992

Other (OTH) AF: 0.102 AC: 215 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital myasthenic syndrome 11 (2)
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	Congenital myasthenic syndrome 11;C4760576:Fetal akinesia deformation sequence 2 (1)
-	-	1	Fetal akinesia deformation sequence 1 (1)
-	-	1	Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 (1)
-	-	1	Fetal akinesia deformation sequence 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.88
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45603036; hg19: chr11-47463220; COSMIC: COSV54085857;