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Skeletal dysplasia

Gene: RINT1

Amber List (moderate evidence)

RINT1 (RAD50 interactor 1)
EnsemblGeneIds (GRCh38): ENSG00000135249
EnsemblGeneIds (GRCh37): ENSG00000135249
OMIM: 610089, Gene2Phenotype
RINT1 is in 4 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. 3 cases with compound het variants in this gene.
Created: 20 Jan 2021, 11:14 a.m. | Last Modified: 20 Jan 2021, 11:14 a.m.
Panel Version: 2.48
Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Created: 20 Jan 2021, 11:11 a.m. | Last Modified: 27 Jan 2021, 4:24 p.m.
Panel Version: 2.76

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844

Publications

Dmitrijs Rots (RadboudUMC)

Green List (high evidence)

Reported in 3 patients with similar phenotype in PMID: 31204009. Caused by one LoF allele and missense/in-frame hypomorphic allele.
Sources: Literature
Created: 14 Oct 2020, 4:26 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
liver failure; short stature; skeletal abnormalities

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • liver failure
  • short stature
  • skeletal abnormalities
  • Infantile liver failure syndrome 3 OMIM:618641
  • infantile liver failure syndrome 3 MONDO:0032844
Tags
for-review
OMIM
610089
Clinvar variants
Variants in RINT1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Jan 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: RINT1 were changed from liver failure; short stature; skeletal abnormalities to liver failure; short stature; skeletal abnormalities; Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844

20 Jan 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: RINT1 were set to PMID: 31204009

20 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: rint1 has been classified as Amber List (Moderate Evidence).

20 Jan 2021, Gel status: 0

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: RINT1.

14 Oct 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Dmitrijs Rots (RadboudUMC)

gene: RINT1 was added gene: RINT1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RINT1 were set to PMID: 31204009 Phenotypes for gene: RINT1 were set to liver failure; short stature; skeletal abnormalities Penetrance for gene: RINT1 were set to Complete Review for gene: RINT1 was set to GREEN gene: RINT1 was marked as current diagnostic