Genetic Variant RIMS3:c.*1062A>G (chr1-40625455-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970

Publications

9 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RIMS3	NM_014747.3 link	c.*1062A>G	3_prime_UTR_variant	Exon 8 of 8	ENST00000372684.8	NP_055562.2	Q9UJD0-1
RIMS3	XM_047435184.1 link	c.*1062A>G	3_prime_UTR_variant	Exon 11 of 11		XP_047291140.1
RIMS3	XM_047435189.1 link	c.*1062A>G	3_prime_UTR_variant	Exon 8 of 8		XP_047291145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS3	ENST00000372684.8 link	c.*1062A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_014747.3	ENSP00000361769.3		Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119294

AN:

151898

Hom.:

47366

Cov.:

show subpopulations

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.:

AF XY:

0.801

AC XY:

197

AN XY:

246

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.795

AC:

280

AN:

352

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.785

AC:

119383

AN:

152016

Hom.:

47405

Cov.:

AF XY:

0.778

AC XY:

57802

AN XY:

74294

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1243

2485

3728

4970

6213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.8

(source)

DANN

Benign

0.73

PhyloP100

0.097

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over