Genetic Variant RIN3:p.Pro186Thr (chr14-92651605-C-A) – 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_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. 16/22 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

Publications

0 publications found

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 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=0.0935497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024832.5. 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
	RIN3	NM_024832.5	MANE Select	c.556C>A	p.Pro186Thr	missense	Exon 6 of 10	NP_079108.3
	RIN3	NM_001319987.2		c.331C>A	p.Pro111Thr	missense	Exon 5 of 9	NP_001306916.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIN3	ENST00000216487.12	TSL:1 MANE Select	c.556C>A	p.Pro186Thr	missense	Exon 6 of 10	ENSP00000216487.7	Q8TB24-1
RIN3	ENST00000555589.5	TSL:1	n.*3C>A		non_coding_transcript_exon	Exon 5 of 9	ENSP00000450682.1	G3V2I7
RIN3	ENST00000555589.5	TSL:1	n.*3C>A		3_prime_UTR	Exon 5 of 9	ENSP00000450682.1	G3V2I7

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

246992

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:

0.00000357

AC:

AN:

1399150

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694130

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31586

American (AMR)

AF:

0.0000238

AC:

AN:

41974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23772

East Asian (EAS)

AF:

0.00

AC:

AN:

35466

South Asian (SAS)

AF:

0.00

AC:

AN:

85500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069928

Other (OTH)

AF:

0.0000178

AC:

AN:

56262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

AF:

0.0000467

AC:

AN:

149974

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

73246

show subpopulations

African (AFR)

AF:

0.0000977

AC:

AN:

40960

American (AMR)

AF:

0.000199

AC:

AN:

15084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

4912

South Asian (SAS)

AF:

0.00

AC:

AN:

4574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67468

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.7

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.52

M_CAP

Benign

0.0066

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.40

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

REVEL

Benign

0.042

Sift

Benign

0.32

Sift4G

Benign

0.18

Polyphen

0.0040

Vest4

0.14

MutPred

0.30

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

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over