U.S. flag

An official website of the United States government

NM_052859.4(RFT1):c.454A>G (p.Lys152Glu) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 19, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001818462.4

Allele description [Variation Report for NM_052859.4(RFT1):c.454A>G (p.Lys152Glu)]

NM_052859.4(RFT1):c.454A>G (p.Lys152Glu)

Gene:
RFT1:RFT1 homolog [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.1
Genomic location:
Preferred name:
NM_052859.4(RFT1):c.454A>G (p.Lys152Glu)
HGVS:
  • NC_000003.12:g.53122376T>C
  • NG_009203.1:g.13079A>G
  • NM_052859.4:c.454A>GMANE SELECT
  • NP_443091.1:p.Lys152Glu
  • NC_000003.11:g.53156392T>C
  • NM_052859.2:c.454A>G
  • NM_052859.3:c.454A>G
  • Q96AA3:p.Lys152Glu
Protein change:
K152E; LYS152GLU
Links:
UniProtKB: Q96AA3#VAR_062572; OMIM: 611908.0002; dbSNP: rs763862849
NCBI 1000 Genomes Browser:
rs763862849
Molecular consequence:
  • NM_052859.4:c.454A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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
SCV002064543Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 19, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002064543.1

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

Description

DNA sequence analysis of the RFT1 gene demonstrated a sequence change, c.454A>G, in exon 4 that results in an amino acid change, p.Lys152Glu. This sequence change has been previously described in two patients in the homozygous state with neurological and clinical features of RFT1-related disorder (PMIDs: 19856127, 19701946). Expression of wild-type RFT1 in the patients? fibroblasts showed complementation of the abnormal lipid-linked oligosaccharide profile and reduced DNase 1 secretion, supporting RFT1 defect (PMID: 19701946). This sequence change has been described in the gnomAD database with a low population frequency of 0.0052% (dbSNP rs763862849). The p.Lys152Glu change affects a highly conserved amino acid residue located in a domain of the RFT1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Lys152Glu substitution. These collective evidences indicate that this sequence change is pathogenic.

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

Last Updated: Feb 20, 2024