Genetic Variant NM_014989.7:c.49C>G (chr6-71887072-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014989.7(RIMS1):c.49C>G(p.Pro17Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RIMS1
NM_014989.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.22

Publications

0 publications found

Variant links:

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

RIMS1 Gene-Disease associations (from GenCC):

cone-rod dystrophy 7
Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Illumina

RIMS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19733286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014989.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RIMS1	NM_014989.7	MANE Select	c.49C>G	p.Pro17Ala	missense	Exon 1 of 34	NP_055804.2
RIMS1	NM_001350413.1		c.49C>G	p.Pro17Ala	missense	Exon 1 of 4	NP_001337342.1
RIMS1	NM_001350411.1		c.49C>G	p.Pro17Ala	missense	Exon 1 of 4	NP_001337340.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.49C>G	p.Pro17Ala	missense	Exon 1 of 34	ENSP00000428417.1	Q86UR5-1
RIMS1	ENST00000264839.11	TSL:5	c.49C>G	p.Pro17Ala	missense	Exon 1 of 30	ENSP00000264839.7	Q86UR5-4
RIMS1	ENST00000697193.1		c.49C>G	p.Pro17Ala	missense	Exon 1 of 29	ENSP00000513179.1	A0A8V8TKU9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

247244

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111616

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.067

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

PhyloP100

4.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.1

REVEL

Benign

0.073

Sift

Benign

0.46

Sift4G

Benign

0.36

Polyphen

0.97

Vest4

0.38

MutPred

0.17

Loss of glycosylation at P17 (P = 0.0162)

MVP

0.61

MPC

1.4

ClinPred

0.68

GERP RS

4.6

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.17

gMVP

0.61

Mutation Taster

=95/5

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over