1-40620552-C-T

Variant names:

• chr1-40620552-C-T
• rs12125724
• NM_014747.3:c.*5965G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS3	NM_014747.3	MANE Select	c.*5965G>A		downstream_gene	N/A	NP_055562.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS3	ENST00000372684.8	TSL:1 MANE Select	c.*5965G>A		downstream_gene	N/A	ENSP00000361769.3
	RIMS3	ENST00000858245.1		c.*5965G>A		downstream_gene	N/A	ENSP00000528304.1
	RIMS3	ENST00000858246.1		c.*5965G>A		downstream_gene	N/A	ENSP00000528305.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73765 AN: 151968 Hom.: 19984 Cov.: 32

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: 92 AN: 224 Hom.: 16 AF XY: 0.413 AC XY: 57 AN XY: 138

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.407 AC: 74 AN: 182

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.438 AC: 14 AN: 32

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.486 AC: 73864 AN: 152086 Hom.: 20027 Cov.: 32 AF XY: 0.484 AC XY: 35985 AN XY: 74344

African (AFR) AF: 0.741 AC: 30750 AN: 41486

American (AMR) AF: 0.376 AC: 5747 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1084 AN: 5182

South Asian (SAS) AF: 0.411 AC: 1982 AN: 4818

European-Finnish (FIN) AF: 0.432 AC: 4567 AN: 10562

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27244 AN: 67962

Other (OTH) AF: 0.443 AC: 937 AN: 2116

Alfa AF: 0.385 Hom.: 2568

Bravo AF: 0.489

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12125724; hg19: chr1-41086224;