Variant chr14-92651605-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024832.5(RIN3):c.556C>A(p.Pro186Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000775 in 1,549,124 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 0.000047 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

RIN3
NM_024832.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.396

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0935497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5 linkuse as main transcript	c.556C>A	p.Pro186Thr	missense_variant	6/10	ENST00000216487.12
RIN3	NM_001319987.2 linkuse as main transcript	c.331C>A	p.Pro111Thr	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12 linkuse as main transcript	c.556C>A	p.Pro186Thr	missense_variant	6/10	1	NM_024832.5	P2	Q8TB24-1

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

149974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000977

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

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

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399150

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694130

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000238

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:

9.35e-7

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000467

AC:

AN:

149974

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

73246

show subpopulations

Gnomad4 AFR

AF:

0.0000977

Gnomad4 AMR

AF:

0.000199

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

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

Jul 17, 2023

The c.556C>A (p.P186T) alteration is located in exon 6 (coding exon 6) of the RIN3 gene. This alteration results from a C to A substitution at nucleotide position 556, causing the proline (P) at amino acid position 186 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.7

DANN

Benign

0.76

DEOGEN2

Benign

0.0033

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.042

Sift

Benign

0.32

T;.

Sift4G

Benign

0.18

T;T

Polyphen

0.0040

B;.

Vest4

0.14

MutPred

0.30

Loss of catalytic residue at P186 (P = 0.0172);Loss of catalytic residue at P186 (P = 0.0172);

MVP

0.48

MPC

0.29

ClinPred

0.26

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.35

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