rs1048200516

Variant names:

• chr11-47438779-C-T
• rs1048200516
• NM_005055.5:c.1119G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47438779-C-T
• chr11-47438779-C-A
• chr11-47438779-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001440490.1(RAPSN):​c.1255G>A​(p.Glu419Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,415,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RAPSN NM_001440490.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.166).
• BP6: Variant 11-47438779-C-T is Benign according to our data. Variant chr11-47438779-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 476116.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440490.1. 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.1119G>A	p.Lys373Lys	synonymous	Exon 7 of 8	NP_005046.2
	RAPSN	NM_001440490.1		c.1255G>A	p.Glu419Lys	missense	Exon 7 of 8	NP_001427419.1
	RAPSN	NM_001440491.1		c.1204G>A	p.Glu402Lys	missense	Exon 7 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.1119G>A	p.Lys373Lys	synonymous	Exon 7 of 8	ENSP00000298854.2	Q13702-1
	RAPSN	ENST00000352508.7	TSL:1	c.942G>A	p.Lys314Lys	synonymous	Exon 5 of 6	ENSP00000298853.3	Q13702-2
	RAPSN	ENST00000529341.1	TSL:1	c.942G>A	p.Lys314Lys	synonymous	Exon 5 of 5	ENSP00000431732.1	E9PK11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000105 AC: 2 AN: 190314 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1415186 Hom.: 0 Cov.: 34 AF XY: 0.00000287 AC XY: 2 AN XY: 697972

African (AFR) AF: 0.00 AC: 0 AN: 32812

American (AMR) AF: 0.0000758 AC: 3 AN: 39602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 37804

South Asian (SAS) AF: 0.00 AC: 0 AN: 80784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084472

Other (OTH) AF: 0.00 AC: 0 AN: 58424

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.6
DANN	Uncertain	0.98
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1048200516; hg19: chr11-47460330; COSMIC: COSV100100311;