Variant 11-8168916-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001206671.4(RIC3):c.74A>G(p.Lys25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,611,858 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

RIC3
NM_001206671.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011424035).

BP6

Variant 11-8168916-T-C is Benign according to our data. Variant chr11-8168916-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3043381.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC3	NM_001206671.4 linkuse as main transcript	c.74A>G	p.Lys25Arg	missense_variant	1/6	ENST00000309737.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC3	ENST00000309737.11 linkuse as main transcript	c.74A>G	p.Lys25Arg	missense_variant	1/6	1	NM_001206671.4	A1	Q7Z5B4-1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00125

AC:

308

AN:

247126

Hom.:

AF XY:

0.00118

AC XY:

158

AN XY:

134218

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000931

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00250

GnomAD4 exome

AF:

0.00162

AC:

2367

AN:

1459640

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1141

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.00178

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152218

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00114

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00132

AC:

160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RIC3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 12, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.88

D;T;T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.65

N;N;N;N;.;N

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.070

Sift

Pathogenic

0.0

D;T;T;T;T;T

Sift4G

Pathogenic

0.0

D;T;T;T;.;T

Polyphen

0.51

P;B;B;.;.;B

Vest4

0.18

MVP

0.39

MPC

0.13

ClinPred

0.091

GERP RS

4.3

Varity_R

0.061

gMVP

0.47

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