Variant 1-40628830-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_014747.3(RIMS3):c.694C>T(p.Pro232Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,160 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 (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P232L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

RIMS3
NM_014747.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 9.94

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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017132789).

BP6

Variant 1-40628830-G-A is Benign according to our data. Variant chr1-40628830-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3356146.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RIMS3	NM_014747.3 linkuse as main transcript	c.694C>T	p.Pro232Ser	missense_variant	7/8	ENST00000372684.8
RIMS3	XM_047435184.1 linkuse as main transcript	c.694C>T	p.Pro232Ser	missense_variant	10/11
RIMS3	XM_047435189.1 linkuse as main transcript	c.694C>T	p.Pro232Ser	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8 linkuse as main transcript	c.694C>T	p.Pro232Ser	missense_variant	7/8	1	NM_014747.3	P1	Q9UJD0-1
RIMS3	ENST00000372683.1 linkuse as main transcript	c.694C>T	p.Pro232Ser	missense_variant	7/8	1		P1	Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000366

AC:

AN:

251380

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00324

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000414

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000609

Hom.:

Bravo

AF:

0.000363

ExAC

AF:

0.000321

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RIMS3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2024

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

Uncertain

0.36

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

.;D

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-7.7

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.19

T;T

Sift4G

Benign

0.18

T;T

Polyphen

1.0

D;D

Vest4

0.66

MVP

0.92

MPC

1.1

ClinPred

0.19

GERP RS

4.8

Varity_R

0.59

gMVP

0.49

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