dbSNP rs74074811: RIN3:p.Arg427Gln (chr14-92652329-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024832.5(RIN3):c.1280G>A(p.Arg427Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,604,332 control chromosomes in the GnomAD database, including 1,178 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 549 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 629 hom. )

Consequence

RIN3
NM_024832.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.773

Variant links:

Genes affected

RIN3 (HGNC:18751): (Ras and Rab interactor 3) Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RIN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012609661).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN3	NM_024832.5 link	c.1280G>A	p.Arg427Gln	missense_variant	Exon 6 of 10	ENST00000216487.12	NP_079108.3	Q8TB24-1Q6NSK7Q86U22
RIN3	NM_001319987.2 link	c.1055G>A	p.Arg352Gln	missense_variant	Exon 5 of 9		NP_001306916.1	Q8TB24Q6ZRC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12 link	c.1280G>A	p.Arg427Gln	missense_variant	Exon 6 of 10	1	NM_024832.5	ENSP00000216487.7		Q8TB24-1

Frequencies

GnomAD3 genomes

AF:

0.0476

AC:

7244

AN:

152044

Hom.:

549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.0293

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0415

GnomAD3 exomes

AF:

0.0200

AC:

4888

AN:

243820

Hom.:

247

AF XY:

0.0182

AC XY:

2391

AN XY:

131596

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.00710

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.0348

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000865

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.00819

AC:

11892

AN:

1452170

Hom.:

629

Cov.:

AF XY:

0.00857

AC XY:

6178

AN XY:

721232

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.00861

Gnomad4 ASJ exome

AF:

0.00496

Gnomad4 EAS exome

AF:

0.0240

Gnomad4 SAS exome

AF:

0.0401

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000518

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0477

AC:

7251

AN:

152162

Hom.:

549

Cov.:

AF XY:

0.0463

AC XY:

3441

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.0288

Gnomad4 SAS

AF:

0.0441

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0411

Alfa

AF:

0.0201

Hom.:

112

Bravo

AF:

0.0523

ESP6500AA

AF:

0.146

AC:

643

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0230

AC:

2790

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0070

DANN

Benign

0.63

DEOGEN2

Benign

0.00065

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.7

N;.

PrimateAI

Benign

0.16

PROVEAN

Benign

0.15

N;.

REVEL

Benign

0.011

Sift

Benign

0.80

T;.

Sift4G

Benign

0.76

T;T

Polyphen

0.041

B;.

Vest4

0.048

MPC

0.31

ClinPred

0.0065

GERP RS

-6.8

Varity_R

0.016

gMVP

0.091

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over