rs201124957

Variant names:

• chr11-47442706-C-A
• NM_005055.5:c.640G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47442706-C-A
• chr11-47442706-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RAPSN NM_005055.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50

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]

LOC124902673 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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
RAPSN	NM_005055.5	c.640G>T	p.Val214Leu	missense_variant	Exon 3 of 8	ENST00000298854.7	NP_005046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7	c.640G>T	p.Val214Leu	missense_variant	Exon 3 of 8	1	NM_005055.5	ENSP00000298854.2
RAPSN	ENST00000352508.7	c.640G>T	p.Val214Leu	missense_variant	Exon 3 of 6	1		ENSP00000298853.3
RAPSN	ENST00000529341.1	c.640G>T	p.Val214Leu	missense_variant	Exon 3 of 5	1		ENSP00000431732.1
RAPSN	ENST00000524487.5	c.532-785G>T		intron_variant	Intron 2 of 6	5		ENSP00000435551.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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;.
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47464258;