NM_153704.6(TMEM67):c.2498T>C (p.Ile833Thr) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Nov 20, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000821785.2

Allele description [Variation Report for NM_153704.6(TMEM67):c.2498T>C (p.Ile833Thr)]

NM_153704.6(TMEM67):c.2498T>C (p.Ile833Thr)

Gene:
TMEM67:transmembrane protein 67 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q22.1
Genomic location:
Preferred name:
NM_153704.6(TMEM67):c.2498T>C (p.Ile833Thr)
HGVS:
  • NC_000008.11:g.93808898T>C
  • NG_009190.1:g.59055T>C
  • NM_001142301.1:c.2255T>C
  • NM_153704.5:c.2498T>C
  • NM_153704.6:c.2498T>CMANE SELECT
  • NP_001135773.1:p.Ile752Thr
  • NP_714915.3:p.Ile833Thr
  • NP_714915.3:p.Ile833Thr
  • LRG_688t1:c.2498T>C
  • LRG_688t2:c.2255T>C
  • LRG_688:g.59055T>C
  • LRG_688p1:p.Ile833Thr
  • LRG_688p2:p.Ile752Thr
  • NC_000008.10:g.94821126T>C
  • NR_024522.2:n.2519T>C
  • Q5HYA8:p.Ile833Thr
Protein change:
I752T; ILE833THR
Links:
UniProtKB: Q5HYA8#VAR_063801; OMIM: 609884.0013; dbSNP: rs267607119
NCBI 1000 Genomes Browser:
rs267607119
Molecular consequence:
  • NM_001142301.1:c.2255T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153704.5:c.2498T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153704.6:c.2498T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_024522.2:n.2519T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Joubert syndrome (JBTS)
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300; Human Phenotype Ontology: HP:0002335
Name:
Meckel-Gruber syndrome
Synonyms:
DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:
MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000962554Invitaecriteria provided, single submitter
Pathogenic
(Nov 20, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management.

Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, He W, Dharmadhikari AV, Qu C, Ward P, Braxton A, Narayanan S, Ge X, Tokita MJ, Santiago-Sim T, Dai H, Chiang T, Smith H, Azamian MS, Robak L, Bostwick BL, et al.

JAMA Pediatr. 2017 Dec 4;171(12):e173438. doi: 10.1001/jamapediatrics.2017.3438. Epub 2017 Dec 4.

PubMed [citation]
PMID:
28973083
PMCID:
PMC6359927

Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.

Chaki M, Hoefele J, Allen SJ, Ramaswami G, Janssen S, Bergmann C, Heckenlively JR, Otto EA, Hildebrandt F.

Kidney Int. 2011 Dec;80(11):1239-45. doi: 10.1038/ki.2011.284. Epub 2011 Aug 24.

PubMed [citation]
PMID:
21866095
PMCID:
PMC4037742
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000962554.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces isoleucine with threonine at codon 833 of the TMEM67 protein (p.Ile833Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs267607119, ExAC 0.006%). This variant has been observed to segregate with Joubert syndrome in families (PMID: 19058225, 21866095) and has also been observed in individuals with Joubert syndrome (PMID: 19058225, 21866095, 26092869, 28497568, 28973083). ClinVar contains an entry for this variant (Variation ID: 1378). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 6, 2021

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