Genetic Variant RIN1:p.Arg608Pro (chr11-66333310-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004292.3(RIN1):c.1823G>C(p.Arg608Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,264 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. R608H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RIN1
NM_004292.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.238

Publications

0 publications found

Variant links:

Genes affected

RIN1 (HGNC:18749): (Ras and Rab interactor 1) Predicted to enable small GTPase binding activity. Predicted to be involved in endocytosis; regulation of catalytic activity; and signal transduction. Predicted to act upstream of or within associative learning; memory; and negative regulation of synaptic plasticity. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RIN1 Gene-Disease associations (from GenCC):

familial nonmedullary thyroid carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RIN1 links:

ENSG00000254756 (HGNC:):

ENSG00000254756 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3940475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIN1	NM_004292.3	MANE Select	c.1823G>C	p.Arg608Pro	missense	Exon 9 of 10	NP_004283.2	A0A0S2Z4U0
RIN1	NM_001363559.2		c.1739G>C	p.Arg580Pro	missense	Exon 9 of 10	NP_001350488.1
RIN1	NM_001363560.2		c.1637G>C	p.Arg546Pro	missense	Exon 9 of 10	NP_001350489.1	Q13671-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIN1	ENST00000311320.9	TSL:1 MANE Select	c.1823G>C	p.Arg608Pro	missense	Exon 9 of 10	ENSP00000310406.4	Q13671-1
RIN1	ENST00000970357.1		c.1670G>C	p.Arg557Pro	missense	Exon 9 of 10	ENSP00000640416.1
RIN1	ENST00000869551.1		c.1637G>C	p.Arg546Pro	missense	Exon 9 of 10	ENSP00000539610.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460264

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5128

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.0029

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.0087

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

PhyloP100

0.24

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.53

REVEL

Benign

0.17

Sift

Benign

0.077

Sift4G

Benign

0.081

Polyphen

0.99

Vest4

0.74

MutPred

0.43

Loss of MoRF binding (P = 0.0277)

MVP

0.22

MPC

0.52

ClinPred

0.28

GERP RS

2.2

Varity_R

0.17

gMVP

0.82

Mutation Taster

=79/21

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over