dbSNP rs7520333: RIMS3:c.*1939T>C (chr1-40624578-A-G) – 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.*1939T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,026 control chromosomes in the GnomAD database, including 19,493 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 ( 19490 hom., cov: 31)

Exomes 𝑓: 0.54 ( 3 hom. )

Consequence

RIMS3
NM_014747.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.491

Publications

13 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:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RIMS3	NM_014747.3 link	c.*1939T>C	3_prime_UTR_variant	Exon 8 of 8	ENST00000372684.8	NP_055562.2	Q9UJD0-1
RIMS3	XM_047435184.1 link	c.*1939T>C	3_prime_UTR_variant	Exon 11 of 11		XP_047291140.1
RIMS3	XM_047435189.1 link	c.*1939T>C	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.*1939T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_014747.3	ENSP00000361769.3		Q9UJD0-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74647

AN:

151882

Hom.:

19466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.461

GnomAD4 exome

AF:

0.538

AC:

AN:

Hom.:

Cov.:

AF XY:

0.538

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.600

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.492

AC:

74712

AN:

152000

Hom.:

19490

Cov.:

AF XY:

0.489

AC XY:

36301

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.662

AC:

27428

AN:

41438

American (AMR)

AF:

0.390

AC:

5965

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1361

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1055

AN:

5160

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4818

European-Finnish (FIN)

AF:

0.488

AC:

5157

AN:

10564

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30626

AN:

67964

Other (OTH)

AF:

0.457

AC:

962

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1875

3750

5626

7501

9376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.458

Hom.:

27592

Bravo

AF:

0.489

Asia WGS

AF:

0.316

AC:

1097

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.40

PhyloP100

0.49

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

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rs7520333

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over