Genetic Variant 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.

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.*1939T>C		3_prime_UTR	Exon 8 of 8	NP_055562.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIMS3	ENST00000372684.8	TSL:1 MANE Select	c.*1939T>C	3_prime_UTR	Exon 8 of 8	ENSP00000361769.3	Q9UJD0-1
RIMS3	ENST00000858245.1		c.*1939T>C	3_prime_UTR	Exon 7 of 7	ENSP00000528304.1
RIMS3	ENST00000858246.1		c.*1939T>C	3_prime_UTR	Exon 9 of 9	ENSP00000528305.1

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.458

Hom.:

27592

Bravo

AF:

0.489

Asia WGS

AF:

0.316

AC:

1097

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over