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NM_018840.5(RAB5IF):c.75G>A (p.Trp25Ter) AND Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 1, 2014
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002267636.3

Allele description [Variation Report for NM_018840.5(RAB5IF):c.75G>A (p.Trp25Ter)]

NM_018840.5(RAB5IF):c.75G>A (p.Trp25Ter)

Genes:
LOC130065793:ATAC-STARR-seq lymphoblastoid silent region 12876 [Gene]
RAB5IF:RAB5 interacting factor [Gene - OMIM - HGNC]
TGIF2-RAB5IF:TGIF2-RAB5IF readthrough [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q11.23
Genomic location:
Preferred name:
NM_018840.5(RAB5IF):c.75G>A (p.Trp25Ter)
HGVS:
  • NC_000020.11:g.36606026G>A
  • NG_200210.1:g.354G>A
  • NM_001199534.2:c.75G>A
  • NM_001199535.2:c.193-1689G>A
  • NM_001374178.1:c.75G>A
  • NM_018840.5:c.75G>AMANE SELECT
  • NM_199483.3:c.75G>A
  • NP_001186463.1:p.Trp25Ter
  • NP_001361107.1:p.Trp25Ter
  • NP_061328.1:p.Trp25Ter
  • NP_955777.1:p.Trp25Ter
  • NC_000020.10:g.35234429G>A
  • NM_018840.5:c.75G>A
  • NR_026562.4:n.248G>A
  • NR_164350.1:n.248G>A
  • NR_164351.1:n.248G>A
  • p.Trp25Ter
Protein change:
W25*; TRP25TER
Links:
OMIM: 619960.0001; dbSNP: rs1464308137
NCBI 1000 Genomes Browser:
rs1464308137
Molecular consequence:
  • NM_001199535.2:c.193-1689G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NR_026562.4:n.248G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_164350.1:n.248G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_164351.1:n.248G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001199534.2:c.75G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374178.1:c.75G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_018840.5:c.75G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_199483.3:c.75G>A - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
absent gene product [Sequence Ontology: SO:0002317]

Condition(s)

Name:
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2 (CFSMR2)
Identifiers:
MONDO: MONDO:0859567; MedGen: C5676895; OMIM: 616994

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002549757OMIM
no assertion criteria provided
Pathogenic
(Feb 1, 2014) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia.

Alanay Y, Ergüner B, Utine E, Haçariz O, Kiper PO, Taşkıran EZ, Perçin F, Uz E, Sağiroğlu MŞ, Yuksel B, Boduroglu K, Akarsu NA.

Am J Med Genet A. 2014 Feb;164A(2):291-304. doi: 10.1002/ajmg.a.36248. Epub 2013 Nov 5. Review.

PubMed [citation]
PMID:
24194475

Defining mitochondrial protein functions through deep multiomic profiling.

Rensvold JW, Shishkova E, Sverchkov Y, Miller IJ, Cetinkaya A, Pyle A, Manicki M, Brademan DR, Alanay Y, Raiman J, Jochem A, Hutchins PD, Peters SR, Linke V, Overmyer KA, Salome AZ, Hebert AS, Vincent CE, Kwiecien NW, Rush MJP, Westphall MS, Craven M, et al.

Nature. 2022 Jun;606(7913):382-388. doi: 10.1038/s41586-022-04765-3. Epub 2022 May 25.

PubMed [citation]
PMID:
35614220
PMCID:
PMC9310563

Details of each submission

From OMIM, SCV002549757.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a Turkish boy with craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome (CFSMR2; 616994), who was originally studied by Alanay et al. (2014) (family 5), Rensvold et al. (2022) identified homozygosity for a c.75G-A transition in exon 1 of the RAB5IF gene, resulting in a trp25-to-ter (W25X) substitution that was not found in the gnomAD database. Segregation analysis in the multiply consanguineous Turkish family revealed 4 unaffected individuals who were heterozygous for the mutation, including the proband's parents, a paternal aunt, and a cousin; the father and cousin had cleft lip/palate. HAP1 cells engineered to express the W25X RAB5IF mutation showed loss of TMCO1 (614123), and full proteomic analysis of 2 independent clones harboring the mutation demonstrated that TMCO1 was the most affected protein in each case. In addition, patient fibroblasts exhibited loss of RAB5IF and TMCO1, and transfection of wildtype RAB5IF into the cells resulted in a substantial increase in TMCO1 levels.

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

Last Updated: Dec 14, 2024