Variant chr14-92651612-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024832.5(RIN3):c.563A>C(p.Gln188Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,605,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

RIN3
NM_024832.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.706

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024585873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIN3	NM_024832.5 linkuse as main transcript	c.563A>C	p.Gln188Pro	missense_variant	6/10	ENST00000216487.12	NP_079108.3
RIN3	NM_001319987.2 linkuse as main transcript	c.338A>C	p.Gln113Pro	missense_variant	5/9		NP_001306916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12 linkuse as main transcript	c.563A>C	p.Gln188Pro	missense_variant	6/10	1	NM_024832.5	ENSP00000216487	P2	Q8TB24-1

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

149686

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000725

AC:

AN:

248206

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134498

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000530

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000137

AC:

AN:

1456008

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

724020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000454

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000200

AC:

AN:

149686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72980

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2022

The c.563A>C (p.Q188P) alteration is located in exon 6 (coding exon 6) of the RIN3 gene. This alteration results from a A to C substitution at nucleotide position 563, causing the glutamine (Q) at amino acid position 188 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.69

DEOGEN2

Benign

0.0034

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.0050

Sift

Benign

0.47

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;.

Vest4

0.084

MutPred

0.29

Gain of glycosylation at Q188 (P = 0.0103);Gain of glycosylation at Q188 (P = 0.0103);

MVP

0.18

MPC

0.32

ClinPred

0.034

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over