NM_000492.3(CFTR):c.1730A>T (p.Tyr577Phe) AND none provided

Clinical significance:Uncertain significance (Last evaluated: Dec 23, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001285536.1

Allele description [Variation Report for NM_000492.3(CFTR):c.1730A>T (p.Tyr577Phe)]

NM_000492.3(CFTR):c.1730A>T (p.Tyr577Phe)

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.3(CFTR):c.1730A>T (p.Tyr577Phe)
HGVS:
  • NC_000007.14:g.117590403A>T
  • NG_016465.4:g.129620A>T
  • NM_000492.3:c.1730A>T
  • NP_000483.3:p.Tyr577Phe
  • LRG_663t1:c.1730A>T
  • LRG_663:g.129620A>T
  • LRG_663p1:p.Tyr577Phe
  • NC_000007.13:g.117230457A>T
Protein change:
Y577F
Links:
dbSNP: rs397508286
NCBI 1000 Genomes Browser:
rs397508286
Molecular consequence:
  • NM_000492.3:c.1730A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001471990ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Dec 23, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001471990.1

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

Description

The CFTR c.1730A>T; p.Tyr577Phe variant (rs39750828) is reported in the literature on the same chromosome as the c.1742dupT variant in an individual affected with cystic fibrosis that also carried the common pathogenic p.Phe508del variant (Stuhrmann 1997). While p.Tyr577Phe has also been reported in an individual with infertility without the linked c.1742dupT variant, it is not clear that the detection methods used in this study would have detected both variants (Morea 2005). The p.Tyr577Phe variant is reported on a single chromosome (1/250312 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. The tyrosine at codon 577 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site, although RNA analyses would be required to confirm this. Given the lack of clinical and functional data, the significance of the p.Tyr577Phe variant is uncertain at this time. References: Morea A et al. Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility. Mol Hum Reprod. 2005 Aug;11(8):607-14. Stuhrmann M et al. Detection of 100% of the CFTR mutations in 63 CF families from Tyrol. Clin Genet. 1997 Oct;52(4):240-6.

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

Last Updated: Sep 6, 2021

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