NM_000492.4(CFTR):c.3154T>G (p.Phe1052Val) AND Inborn genetic diseases

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Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 15, 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:: RCV001018842.1

Allele description

NM_000492.4(CFTR):c.3154T>G (p.Phe1052Val)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
LOC111674472:DNase I hypersensitive sites in introns 16 and 17a of CFTR [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.3154T>G (p.Phe1052Val)

HGVS:

NC_000007.14:g.117611595T>G
NG_016465.4:g.150812T>G
NG_056128.1:g.4649T>G
NG_056128.2:g.4649T>G
NM_000492.4:c.3154T>GMANE SELECT
NP_000483.3:p.Phe1052Val
NP_000483.3:p.Phe1052Val
LRG_663t1:c.3154T>G
LRG_663:g.150812T>G
LRG_663p1:p.Phe1052Val
NC_000007.13:g.117251649T>G
NM_000492.3:c.3154T>G
P13569:p.Phe1052Val
p.(Phe1052Val)

Protein change:

F1052V

Links:

PharmGKB: 1449191708PA165950341; UniProtKB: P13569#VAR_000232; dbSNP: rs150212784

NCBI 1000 Genomes Browser:

rs150212784

Molecular consequence:

NM_000492.4:c.3154T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001180126	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (3/2017))	Pathogenic (Jan 15, 2019)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 18373402, 23974870, 27214204, 27469177, 7683628, 8662892, 8702904, 9521595 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001180126

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (3/2017))

Pathogenic
(Jan 15, 2019)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

CFTR mutations in Turkish and North African cystic fibrosis patients in Europe: implications for screening.

Lakeman P, Gille JJ, Dankert-Roelse JE, Heijerman HG, Munck A, Iron A, Grasemann H, Schuster A, Cornel MC, Ten Kate LP.

Genet Test. 2008 Mar;12(1):25-35. doi: 10.1089/gte.2007.0046.

PubMed [citation]

PMID:: 18373402

Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, Ramalho AS, Amaral MD, Dorfman R, Zielenski J, Masica DL, Karchin R, Millen L, Thomas PJ, Patrinos GP, Corey M, Lewis MH, Rommens JM, Castellani C, Penland CM, Cutting GR.

Nat Genet. 2013 Oct;45(10):1160-7. doi: 10.1038/ng.2745. Epub 2013 Aug 25.

PubMed [citation]

PMID:: 23974870
PMCID:: PMC3874936

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV001180126.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (8)

Description

The p.F1052V pathogenic mutation (also known as c.3154T>G), located in coding exon 20 of the CFTR gene, results from a T to G substitution at nucleotide position 3154. The phenylalanine at codon 1052 is replaced by valine, an amino acid with highly similar properties. The p.F1052V alteration has been reported as a variant of varying clinical consequences (VVCC) and has been identified in trans with a pathogenic mutation in individuals with intermediate or normal sweat chloride levels, pancreatic sufficiency, and negative for Pseudomonas infection (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7; Salinas DB et al. PLoS ONE, 2016 May;11:e0155624; Sosnay PR et al. Pediatr. Clin. North Am., 2016 08;63:585-98). It has also been reported in the homozygous state and in trans with a pathogenic mutation in individuals with cystic fibrosis (Onay T et al. Hum. Genet., 1998 Feb;102:224-30; Lakeman P et al. Genet. Test., 2008 Mar;12:25-35). In vitro studies demonstrated that the p.F1052V mutant protein is able to mature normally but has reduced activity compared to wild-type (Seibert FS et al. J. Biol. Chem., 1996 Jun;271:15139-45; Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 13, 2022

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