VCV000053175.2 - ClinVar

NM_000492.4(CFTR):c.1057C>T (p.Gln353Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000492.4(CFTR):c.1057C>T (p.Gln353Ter)

Variation ID: 53175 Accession: VCV000053175.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117540287 (GRCh38) [ NCBI UCSC ] 7: 117180341 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 16, 2020	Oct 26, 2024	Aug 26, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.1057C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Gln353Ter	nonsense
NC_000007.14:g.117540287C>T
NC_000007.13:g.117180341C>T
NG_016465.4:g.79504C>T
LRG_663:g.79504C>T
LRG_663t1:c.1057C>T	LRG_663p1:p.Gln353Ter

... more HGVS ... less HGVS

Protein change

Q353*

Other names

Canonical SPDI

NC_000007.14:117540286:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA326379 dbSNP: rs397508148 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CFTR		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	3800	6217

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cystic fibrosis	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Aug 26, 2024	RCV001009439.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 29, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	cystic fibrosis	CFTR-France Accession: SCV001169461.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020	Publications: PubMed (1) PubMed: 28603918 Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Pathogenic (Aug 26, 2024) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Cystic fibrosis	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005381807.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Publications: PubMed (1) PubMed: 30938940 Comment: show Variant summary: CFTR c.1057C>T (p.Gln353X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251142 control chromosomes. c.1057C>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Atag_2019). The following publication has been ascertained in the context of this evaluation (PMID: 30938940). ClinVar contains an entry for this variant (Variation ID: 53175). Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Variant summary: CFTR c.1057C>T (p.Gln353X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251142 control chromosomes. c.1057C>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Atag_2019). The following publication has been ascertained in the context of this evaluation (PMID: 30938940). ClinVar contains an entry for this variant (Variation ID: 53175). Based on the evidence outlined above, the variant was classified as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.	Atag E	Pediatric pulmonology	2019	PMID: 30938940

Text-mined citations for rs397508148 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 07, 2025