Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021930.6(RINT1):c.736C>G(p.Pro246Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P246T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

RINT1
NM_021930.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

Publications

0 publications found

Variant links:

Genes affected

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

RINT1 Gene-Disease associations (from GenCC):

infantile liver failure syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
infantile liver failure syndrome 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RINT1 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=0.14295402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021930.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RINT1	NM_021930.6	MANE Select	c.736C>G	p.Pro246Ala	missense	Exon 6 of 15	NP_068749.3
RINT1	NM_001346599.2		c.502C>G	p.Pro168Ala	missense	Exon 6 of 15	NP_001333528.1
RINT1	NR_144478.2		n.851C>G		non_coding_transcript_exon	Exon 6 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RINT1	ENST00000257700.7	TSL:1 MANE Select	c.736C>G	p.Pro246Ala	missense	Exon 6 of 15	ENSP00000257700.2
RINT1	ENST00000467392.5	TSL:3	n.*434C>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000418805.1
RINT1	ENST00000497979.5	TSL:5	n.*341C>G		non_coding_transcript_exon	Exon 6 of 15	ENSP00000420582.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.084

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.39

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.0066

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

2.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.73

REVEL

Benign

0.083

Sift

Benign

0.54

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.31

MutPred

0.30

Loss of glycosylation at P246 (P = 0.0172)

MVP

0.42

MPC

0.18

ClinPred

0.35

GERP RS

4.3

Varity_R

0.046

gMVP

0.24

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.

7-105547230-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over