Variant 1-40635919-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014747.3(RIMS3):c.356G>A(p.Gly119Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G119S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RIMS3
NM_014747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RIMS3	NM_014747.3 linkuse as main transcript	c.356G>A	p.Gly119Asp	missense_variant	4/8	ENST00000372684.8
RIMS3	XM_047435184.1 linkuse as main transcript	c.356G>A	p.Gly119Asp	missense_variant	7/11
RIMS3	XM_047435189.1 linkuse as main transcript	c.356G>A	p.Gly119Asp	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8 linkuse as main transcript	c.356G>A	p.Gly119Asp	missense_variant	4/8	1	NM_014747.3	P1	Q9UJD0-1
RIMS3	ENST00000372683.1 linkuse as main transcript	c.356G>A	p.Gly119Asp	missense_variant	4/8	1		P1	Q9UJD0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460428

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726616

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2023

The c.356G>A (p.G119D) alteration is located in exon 4 (coding exon 2) of the RIMS3 gene. This alteration results from a G to A substitution at nucleotide position 356, causing the glycine (G) at amino acid position 119 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.94

MutPred

0.39

Gain of glycosylation at S114 (P = 0.0884);Gain of glycosylation at S114 (P = 0.0884);

MVP

0.89

MPC

1.2

ClinPred

0.99

GERP RS

5.0

Varity_R

0.84

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over