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NM_000492.4(CFTR):c.3274T>C (p.Tyr1092His) AND not provided

Germline classification:
Uncertain significance (4 submissions)
Last evaluated:
Jan 14, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000588214.22

Allele description [Variation Report for NM_000492.4(CFTR):c.3274T>C (p.Tyr1092His)]

NM_000492.4(CFTR):c.3274T>C (p.Tyr1092His)

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.3274T>C (p.Tyr1092His)
HGVS:
  • NC_000007.14:g.117611715T>C
  • NG_016465.4:g.150932T>C
  • NG_056128.2:g.4769T>C
  • NM_000492.4:c.3274T>CMANE SELECT
  • NP_000483.3:p.Tyr1092His
  • NP_000483.3:p.Tyr1092His
  • LRG_663t1:c.3274T>C
  • LRG_663:g.150932T>C
  • LRG_663p1:p.Tyr1092His
  • NC_000007.13:g.117251769T>C
  • NM_000492.3:c.3274T>C
  • p.Tyr1092His
Protein change:
Y1092H
Links:
dbSNP: rs376968326
NCBI 1000 Genomes Browser:
rs376968326
Molecular consequence:
  • NM_000492.4:c.3274T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000859316Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Uncertain significance
(Jan 22, 2018)
germlineclinical testing

Citation Link,

SCV001472777ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)
Uncertain significance
(Jan 14, 2021)
germlineclinical testing

Citation Link,

SCV001714250Mayo Clinic Laboratories, Mayo Clinic
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Dec 2, 2020)
germlineclinical testing

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

SCV001780144GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Feb 11, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown2not 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 Eurofins Ntd Llc (ga), SCV000859316.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001472777.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CFTR c.3274T>C; p.Tyr1092His variant (rs376968326) is reported in the literature in the compound heterozygous state with a known pathogenic variant in individuals affected with cystic fibrosis (Prontera 2016, Trujillano 2013). This variant is reported in ClinVar (Variation ID: 495930), and is only observed on seven alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The tyrosine at codon 1092 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the limited clinical data and lack of functional data, the significance of the p.Tyr1092His variant is uncertain at this time. References: Prontera P et al. A Clinical and Molecular Survey of 62 Cystic Fibrosis Patients from Umbria (Central Italy) Disclosing a High Frequency (2.4%) of the 2184insA Allele: Implications for Screening. Public Health Genomics. 2016;19(6):336-341. Trujillano D et al. Next generation diagnostics of cystic fibrosis and CFTR-related disorders by targeted multiplex high-coverage resequencing of CFTR. J Med Genet. 2013;50(7):455-462.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714250.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV001780144.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Observed with a pathogenic variant in an individual with cystic fibrosis in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Prontera 2016); This variant is associated with the following publications: (PMID: 23687349, 27728908, 25087612)

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

Last Updated: Sep 29, 2024