NM_005055.5:c.*80G>C

Variant names:

• chr11-47437895-C-G
• rs886048385
• NM_005055.5:c.*80G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005055.5(RAPSN):​c.*80G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,532,564 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: RAPSN NM_005055.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.171
• 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: 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 (REVEL=0.124).

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.*80G>C		3_prime_UTR	Exon 8 of 8	NP_005046.2
	RAPSN	NM_001440490.1		c.1455G>C	p.Trp485Cys	missense	Exon 8 of 8	NP_001427419.1
	RAPSN	NM_001440491.1		c.1404G>C	p.Trp468Cys	missense	Exon 8 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.*80G>C		3_prime_UTR	Exon 8 of 8	ENSP00000298854.2	Q13702-1
	RAPSN	ENST00000352508.7	TSL:1	c.*80G>C		3_prime_UTR	Exon 6 of 6	ENSP00000298853.3	Q13702-2
	RAPSN	ENST00000949301.1		c.*80G>C		3_prime_UTR	Exon 8 of 8	ENSP00000619360.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000435 AC: 6 AN: 1380396 Hom.: 0 Cov.: 27 AF XY: 0.00000733 AC XY: 5 AN XY: 681986

African (AFR) AF: 0.00 AC: 0 AN: 31160

American (AMR) AF: 0.00 AC: 0 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25092

East Asian (EAS) AF: 0.00 AC: 0 AN: 35614

South Asian (SAS) AF: 0.00 AC: 0 AN: 78834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00000470 AC: 5 AN: 1062972

Other (OTH) AF: 0.0000174 AC: 1 AN: 57396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs886048385; hg19: chr11-47459446;