U.S. flag

An official website of the United States government

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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 2021
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:
RCV001813587.2

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:
Hypertelorism
Identifiers:
MedGen: C0020534; OMIM: 145400; Human Phenotype Ontology: HP:0000316
Name:
Micrognathia
Synonyms:
Mandibular hypoplasia
Identifiers:
MedGen: C0025990; Human Phenotype Ontology: HP:0000347
Name:
Scoliosis
Identifiers:
MONDO: MONDO:0005392; MedGen: C0036439; Human Phenotype Ontology: HP:0002650
Name:
Bilateral cleft lip and palate
Identifiers:
MedGen: C1398522
Name:
Rib fusion
Identifiers:
MedGen: C0265695; Human Phenotype Ontology: HP:0000902
Name:
Abnormality of the vertebral column
Identifiers:
MedGen: C4021789; Human Phenotype Ontology: HP:0000925
Name:
Macrocephaly
Synonyms:
Macrocephalus; large head
Identifiers:
MedGen: C2243051; Human Phenotype Ontology: HP:0000256
Name:
Bifid ribs
Identifiers:
MedGen: C4721788; Human Phenotype Ontology: HP:0000892
Name:
Intellectual disability
Synonyms:
Intellectual functioning disability; intellectual disabilities; Intellectual developmental disorder
Identifiers:
MONDO: MONDO:0001071; MeSH: D008607; MedGen: C3714756; Human Phenotype Ontology: HP:0001249
Name:
Flat face
Identifiers:
MedGen: C1853241; Human Phenotype Ontology: HP:0012368

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002059946Gene Mapping Laboratory, Hacettepe University
no assertion criteria provided
Pathogenic
(Jun 1, 2021) 		inheritedresearch

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Turkishinheritedyes1not providednot providednot providednot providedresearch

Details of each submission

From Gene Mapping Laboratory, Hacettepe University, SCV002059946.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Turkish1not providednot providedresearchnot provided

Description

p.Tyr25Ter is a predicted loss-of-function mutation. The absence of RAB5IF protein has been confirmed in primary skin fibroblasts from the affected individual. This is accompanied by loss of TMCO1 protein in the fibroblasts, which leads to CFSMR (MIM 213980) syndrome, and external introduction of RAB5IF rescues TMCO1 protein levels in fibroblasts.

Description

The p.Trp25Ter variant has been reported in one Turkish family of consanguineous parents, was absent in large population studies such as gnomAD. The absence of RAB5IF protein has been confirmed in primary skin fibroblasts from the affected individual. This is accompanied by loss of TMCO1 protein in the fibroblasts, which leads to CFSMR (MIM 213980) syndrome, and external introduction of RAB5IF rescues TMCO1 protein levels in fibroblasts. In summary, predicted loss-of-function mutation in homozygosity and strong functional evidence suggest that this variant is pathogenic, leading to CFSMR.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Dec 14, 2024