1-40625455-T-C

Position:

• chr1-40625455-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS3	NM_014747.3	c.*1062A>G		3_prime_UTR_variant	8/8	ENST00000372684.8
RIMS3	XM_047435184.1	c.*1062A>G		3_prime_UTR_variant	11/11
RIMS3	XM_047435189.1	c.*1062A>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8	c.*1062A>G		3_prime_UTR_variant	8/8	1	NM_014747.3	P1

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

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.833

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

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.771

Alfa AF: 0.785 Hom.: 75749

Bravo AF: 0.787

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.73

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