Variant chr1-40635900-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014747.3(RIMS3):c.359+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,611,386 control chromosomes in the GnomAD database, including 484,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 48431 hom., cov: 32)

Exomes 𝑓: 0.77 ( 436223 hom. )

Consequence

RIMS3
NM_014747.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.369

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-40635900-A-G is Benign according to our data. Variant chr1-40635900-A-G is described in ClinVar as [Benign]. Clinvar id is 1300631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RIMS3	NM_014747.3 linkuse as main transcript	c.359+16T>C	intron_variant	ENST00000372684.8
RIMS3	XM_047435184.1 linkuse as main transcript	c.359+16T>C	intron_variant
RIMS3	XM_047435189.1 linkuse as main transcript	c.359+16T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS3	ENST00000372684.8 linkuse as main transcript	c.359+16T>C		intron_variant		1	NM_014747.3	P1	Q9UJD0-1
RIMS3	ENST00000372683.1 linkuse as main transcript	c.359+16T>C		intron_variant		1		P1	Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.792

AC:

120492

AN:

152080

Hom.:

48389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.735

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.784

GnomAD3 exomes

AF:

0.734

AC:

182815

AN:

249006

Hom.:

68391

AF XY:

0.731

AC XY:

98555

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.652

Gnomad ASJ exome

AF:

0.725

Gnomad EAS exome

AF:

0.562

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.773

Gnomad NFE exome

AF:

0.795

Gnomad OTH exome

AF:

0.748

GnomAD4 exome

AF:

0.769

AC:

1122697

AN:

1459188

Hom.:

436223

Cov.:

AF XY:

0.764

AC XY:

554788

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.905

Gnomad4 AMR exome

AF:

0.660

Gnomad4 ASJ exome

AF:

0.725

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.769

Gnomad4 NFE exome

AF:

0.794

Gnomad4 OTH exome

AF:

0.756

GnomAD4 genome

AF:

0.792

AC:

120583

AN:

152198

Hom.:

48431

Cov.:

AF XY:

0.785

AC XY:

58394

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.900

Gnomad4 AMR

AF:

0.688

Gnomad4 ASJ

AF:

0.735

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.565

Gnomad4 FIN

AF:

0.773

Gnomad4 NFE

AF:

0.793

Gnomad4 OTH

AF:

0.776

Alfa

AF:

0.791

Hom.:

8897

Bravo

AF:

0.795

Asia WGS

AF:

0.572

AC:

1991

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.1

DANN

Benign

0.45

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over