U.S. flag

An official website of the United States government

NM_000492.4(CFTR):c.1731C>T (p.Tyr577=) AND not provided

Germline classification:
Uncertain significance (4 submissions)
Last evaluated:
Feb 2, 2024
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:
RCV001508586.22

Allele description [Variation Report for NM_000492.4(CFTR):c.1731C>T (p.Tyr577=)]

NM_000492.4(CFTR):c.1731C>T (p.Tyr577=)

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.4(CFTR):c.1731C>T (p.Tyr577=)
HGVS:
  • NC_000007.14:g.117590404C>T
  • NG_016465.4:g.129621C>T
  • NM_000492.4:c.1731C>TMANE SELECT
  • NP_000483.3:p.Tyr577=
  • NP_000483.3:p.Tyr577=
  • LRG_663t1:c.1731C>T
  • LRG_663:g.129621C>T
  • LRG_663p1:p.Tyr577=
  • NC_000007.13:g.117230458C>T
  • NM_000492.3:c.1731C>T
  • p.Tyr577=
Links:
dbSNP: rs55928397
NCBI 1000 Genomes Browser:
rs55928397
Molecular consequence:
  • NM_000492.4:c.1731C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
3

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001477819ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)
Uncertain significance
(Dec 3, 2020)
germlineclinical testing

Citation Link,

SCV001714835Mayo Clinic Laboratories, Mayo Clinic
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Feb 2, 2024)
germlineclinical testing

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

SCV003831646Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Feb 18, 2021)
germlineclinical testing

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

SCV004221666Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Uncertain significance
(Oct 11, 2022)
unknownclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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

Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools.

Soukarieh O, Gaildrat P, Hamieh M, Drouet A, Baert-Desurmont S, Frébourg T, Tosi M, Martins A.

PLoS Genet. 2016 Jan;12(1):e1005756. doi: 10.1371/journal.pgen.1005756. Erratum in: PLoS Genet. 2016 Apr 06;12(4):e1005971. doi: 10.1371/journal.pgen.1005971.

PubMed [citation]
PMID:
26761715
PMCID:
PMC4711968
See all PubMed Citations (14)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001477819.2

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

Description

The CFTR c.1731C>T; p.Tyr577Tyr variant (rs55928397), is reported in the literature in an individual affected with cystic fibrosis (SickKids CFTR database). This variant is found in the non-Finnish European population with an overall allele frequency of 0.04% (46/128572 alleles) in the Genome Aggregation Database, and it is reported in ClinVar (Variation ID: 35832). This is a synonymous variant in a weakly conserved nucleotide; however, it occurs in an exonic splicing enhancer element and minigene assays indicate it may lead to increased skipping of exon 12 (Amaral 2004, Fernandez Alanis 2012, Pagani 2005), although this has not been demonstrated in patient cells with this variant. Given the lack of clinical and functional data, the significance of the c.1731C>T variant is uncertain at this time. References: SickKids CFTR database entry for p.Tyr577Tyr: http://www.genet.sickkids.on.ca/cftr/MutationDetailPage.external?sp=755 Amaral MD et al. Quantitative methods for the analysis of CFTR transcripts/splicing variants. J Cyst Fibros. 2004 Aug;3 Suppl 2:17-23. Fernandez Alanis et al. An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects. Hum Mol Genet. 2012 Jun 1;21(11):2389-98. Pagani F et al. Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution. Proc Natl Acad Sci U S A. 2005 May 3;102(18):6368-72.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714835.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

PM2_supporting, PS3

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From Revvity Omics, Revvity, SCV003831646.2

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221666.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

The frequency of this variant in the general population, 0.00036 (46/128572 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in affected individuals with idiopathic chronic pancreatitis (PMIDs: 18687795 (2008) and 25492507 (2015)). Functional studies predict exon 12 skipping and did not show any detectable protein (PMIDs: 15463919 (2004), 22362925 (2012), 22591852 (2012), and 32935393 (2020)). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect CFTR mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Oct 26, 2024