11-47447819-T-C

Position:

• chr11-47447819-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005055.5(RAPSN):​c.524A>G​(p.Gln175Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,670 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 no classification for the single variant (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAPSN NM_005055.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31692308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5	c.524A>G	p.Gln175Arg	missense_variant	2/8	ENST00000298854.7	NP_005046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7	c.524A>G	p.Gln175Arg	missense_variant	2/8	1	NM_005055.5	ENSP00000298854	P1
RAPSN	ENST00000352508.7	c.524A>G	p.Gln175Arg	missense_variant	2/6	1		ENSP00000298853
RAPSN	ENST00000529341.1	c.524A>G	p.Gln175Arg	missense_variant	2/5	1		ENSP00000431732
RAPSN	ENST00000524487.5	c.524A>G	p.Gln175Arg	missense_variant	2/7	5		ENSP00000435551

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459670 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726020

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Benign	0.81
DEOGEN2	Benign	0.038	T;.;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.027
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;T;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.90	L;L;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.91	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.035	B;B;.;B
Vest4		0.52
MutPred		0.46		Loss of methylation at K177 (P = 0.058);Loss of methylation at K177 (P = 0.058);Loss of methylation at K177 (P = 0.058);Loss of methylation at K177 (P = 0.058);
MVP		0.76
MPC		0.44
ClinPred		0.73	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs863224912; hg19: chr11-47469371;