Variant 1-40628824-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_014747.3(RIMS3):c.700G>A(p.Gly234Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,614,152 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

RIMS3
NM_014747.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

RIMS3 (HGNC:21292): (regulating synaptic membrane exocytosis 3) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in several processes, including calcium ion-regulated exocytosis of neurotransmitter; modulation of chemical synaptic transmission; and regulation of synapse organization. Predicted to be located in presynaptic active zone. Predicted to be part of glutamatergic synapse. Predicted to be active in cytoskeleton of presynaptic active zone; postsynaptic cytosol; and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

RIMS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-40628824-C-T is Benign according to our data. Variant chr1-40628824-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042239.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RIMS3	NM_014747.3 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/8	ENST00000372684.8
RIMS3	XM_047435184.1 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	10/11
RIMS3	XM_047435189.1 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/8	1	NM_014747.3	P1	Q9UJD0-1
RIMS3	ENST00000372683.1 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/8	1		P1	Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00248

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00117

AC:

294

AN:

251324

Hom.:

AF XY:

0.00107

AC XY:

146

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00202

AC:

2959

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1420

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00243

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00153

AC:

233

AN:

152274

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00248

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00148

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00105

AC:

128

EpiCase

AF:

0.00218

EpiControl

AF:

0.00279

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RIMS3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

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

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

-0.099

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.77

MVP

0.93

MPC

1.1

ClinPred

0.043

GERP RS

4.9

Varity_R

0.83

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: -5

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