rs7520333

chr1-40624578-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014747.3(RIMS3):c.*1939T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,026 control chromosomes in the GnomAD database, including 19,493 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 (19490 hom., cov: 31)
  • Exomes 𝑓: 0.54 (3 hom.)
• Consequence: RIMS3 NM_014747.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS3	NM_014747.3	c.*1939T>C		3_prime_UTR_variant	8/8	ENST00000372684.8
RIMS3	XM_047435184.1	c.*1939T>C		3_prime_UTR_variant	11/11
RIMS3	XM_047435189.1	c.*1939T>C		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8	c.*1939T>C		3_prime_UTR_variant	8/8	1	NM_014747.3	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74647 AN: 151882 Hom.: 19466 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.538 AC: 14 AN: 26 Hom.: 3 Cov.: 0 AF XY: 0.538 AC XY: 14 AN XY: 26

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.600

GnomAD4 genome AF: 0.492 AC: 74712 AN: 152000 Hom.: 19490 Cov.: 31 AF XY: 0.489 AC XY: 36301 AN XY: 74288

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.457

Alfa AF: 0.452 Hom.: 21476

Bravo AF: 0.489

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.40

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

Other links and lift over

dbSNP: rs7520333; hg19: chr1-41090250; COSMIC: COSV65505492; COSMIC: COSV65505492;