Genetic Variant RIMS3:c.*5965G>A (chr1-40620552-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014747.3(RIMS3):c.*5965G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,310 control chromosomes in the GnomAD database, including 20,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 20027 hom., cov: 32)

Exomes 𝑓: 0.41 ( 16 hom. )

Consequence

RIMS3
NM_014747.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RIMS3	NM_014747.3 link	c.*5965G>A	downstream_gene_variant	ENST00000372684.8	NP_055562.2	Q9UJD0-1
RIMS3	XM_047435184.1 link	c.*5965G>A	downstream_gene_variant		XP_047291140.1
RIMS3	XM_047435189.1 link	c.*5965G>A	downstream_gene_variant		XP_047291145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS3	ENST00000372684.8 link	c.*5965G>A		downstream_gene_variant		1	NM_014747.3	ENSP00000361769.3		Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73765

AN:

151968

Hom.:

19984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.411

AC:

AN:

224

Hom.:

AF XY:

0.413

AC XY:

AN XY:

138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.438

Gnomad4 OTH exome

AF:

0.667

GnomAD4 genome

AF:

0.486

AC:

73864

AN:

152086

Hom.:

20027

Cov.:

AF XY:

0.484

AC XY:

35985

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.374

Hom.:

2353

Bravo

AF:

0.489

Asia WGS

AF:

0.335

AC:

1163

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.2

DANN

Benign

0.31

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over