1-40625455-T-C

Variant names:

• chr1-40625455-T-C
• rs570671
• NM_014747.3:c.*1062A>G

Variant summary

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

The NM_014747.3(RIMS3):​c.*1062A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,412 control chromosomes in the GnomAD database, including 47,531 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 0.79 (47405 hom., cov: 30)
  • Exomes 𝑓: 0.79 (126 hom.)
• Consequence: RIMS3 NM_014747.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS3	NM_014747.3	MANE Select	c.*1062A>G		3_prime_UTR	Exon 8 of 8	NP_055562.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS3	ENST00000372684.8	TSL:1 MANE Select	c.*1062A>G		3_prime_UTR	Exon 8 of 8	ENSP00000361769.3	Q9UJD0-1
	RIMS3	ENST00000858245.1		c.*1062A>G		3_prime_UTR	Exon 7 of 7	ENSP00000528304.1
	RIMS3	ENST00000858246.1		c.*1062A>G		3_prime_UTR	Exon 9 of 9	ENSP00000528305.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119294 AN: 151898 Hom.: 47366 Cov.: 30

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.793 AC: 314 AN: 396 Hom.: 126 Cov.: 0 AF XY: 0.801 AC XY: 197 AN XY: 246

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.795 AC: 280 AN: 352

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 27 AN: 36

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.785 AC: 119383 AN: 152016 Hom.: 47405 Cov.: 30 AF XY: 0.778 AC XY: 57802 AN XY: 74294

African (AFR) AF: 0.874 AC: 36244 AN: 41468

American (AMR) AF: 0.691 AC: 10556 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2862 AN: 5134

South Asian (SAS) AF: 0.566 AC: 2726 AN: 4818

European-Finnish (FIN) AF: 0.767 AC: 8120 AN: 10582

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.793 AC: 53885 AN: 67950

Other (OTH) AF: 0.771 AC: 1628 AN: 2112

Alfa AF: 0.787 Hom.: 176636

Bravo AF: 0.787

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs570671; hg19: chr1-41091127; COSMIC: COSV65503967; COSMIC: COSV65503967;