Variant 11-8140149-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206671.4(RIC3):c.169C>A(p.Pro57Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P57H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RIC3
NM_001206671.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.253

Variant links:

Genes affected

RIC3 (HGNC:30338): (RIC3 acetylcholine receptor chaperone) This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

RIC3 links:

RIC3 (HGNC:):

RIC3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13066995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIC3	NM_001206671.4 linkuse as main transcript	c.169C>A	p.Pro57Thr	missense_variant	2/6	ENST00000309737.11	NP_001193600.1	Q7Z5B4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIC3	ENST00000309737.11 linkuse as main transcript	c.169C>A	p.Pro57Thr	missense_variant	2/6	1	NM_001206671.4	ENSP00000308820.6		Q7Z5B4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251274

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727204

show subpopulations

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:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 26, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

.;T;.;.;.

Eigen

Benign

0.020

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.79

T;T;T;D;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

M;M;M;.;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.5

D;D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;.;D

Polyphen

0.76

P;P;.;.;B

Vest4

0.18

MutPred

0.20

Gain of phosphorylation at P57 (P = 0.0222);Gain of phosphorylation at P57 (P = 0.0222);Gain of phosphorylation at P57 (P = 0.0222);Gain of phosphorylation at P57 (P = 0.0222);Gain of phosphorylation at P57 (P = 0.0222);

MVP

0.60

MPC

0.37

ClinPred

0.44

GERP RS

4.8

Varity_R

0.29

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over