Variant 1-40629338-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_014747.3(RIMS3):c.507C>A(p.Gly169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,614,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

RIMS3
NM_014747.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00400

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 -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-40629338-G-T is Benign according to our data. Variant chr1-40629338-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039796.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RIMS3	NM_014747.3 linkuse as main transcript	c.507C>A	p.Gly169=	synonymous_variant	6/8	ENST00000372684.8
RIMS3	XM_047435184.1 linkuse as main transcript	c.507C>A	p.Gly169=	synonymous_variant	9/11
RIMS3	XM_047435189.1 linkuse as main transcript	c.507C>A	p.Gly169=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8 linkuse as main transcript	c.507C>A	p.Gly169=	synonymous_variant	6/8	1	NM_014747.3	P1	Q9UJD0-1
RIMS3	ENST00000372683.1 linkuse as main transcript	c.507C>A	p.Gly169=	synonymous_variant	6/8	1		P1	Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000410

AC:

103

AN:

251442

Hom.:

AF XY:

0.000397

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000151

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000605

Hom.:

Bravo

AF:

0.000272

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Jun 23, 2021

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

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.7

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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