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

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: Jul 22, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000770985.15

Allele description [Variation Report for NM_000492.4(CFTR):c.3154T>G (p.Phe1052Val)]

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

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
CFTR-AS2:CFTR antisense RNA 2 [Gene - 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_056128.2: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
NG_056128.1:g.4649T>G
NM_000492.3:c.3154T>G
P13569:p.Phe1052Val
p.(Phe1052Val)

Protein change:

F1052V

Links:

UniProtKB: P13569#VAR_000232; dbSNP: rs150212784

Molecular consequence:

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

Observations:

Condition(s)

Name:: Hereditary pancreatitis (PCTT)
Synonyms:: Hereditary chronic pancreatitis; PRSS1-Related Hereditary Pancreatitis
Identifiers:: MONDO: MONDO:0008185; MedGen: C0238339; Orphanet: 676; OMIM: 167800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000897972	Center of Genomic medicine, Geneva, University Hospital of Geneva	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 27, 2018)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002529711	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely pathogenic (Apr 29, 2021)	germline	curation	PubMed (17) [See all records that cite these PMIDs] 18373402, 22892530, 30540547, 29589582, 29168366, 33393655, 24204751, 19885835, 20460946, 17489851, 25704068, 25033378, 32113160, 8662892, 8702904, 23974870, 23891399 Citation Link,
SCV002580737	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV006297003	Department of Molecular Genetics, Istishari Arab Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 22, 2025)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20460946, 17489851, 25704068, 25033378, 11938439, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	2	not provided	not provided	not provided	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

Newborn screening for cystic fibrosis: Polish 4 years' experience with CFTR sequencing strategy.

Sobczyńska-Tomaszewska A, Ołtarzewski M, Czerska K, Wertheim-Tysarowska K, Sands D, Walkowiak J, Bal J, Mazurczak T; NBS CF working group.

Eur J Hum Genet. 2013 Apr;21(4):391-6. doi: 10.1038/ejhg.2012.180. Epub 2012 Aug 15.

PubMed [citation]

PMID:: 22892530
PMCID:: PMC3598320

See all PubMed Citations (19)

Details of each submission

From Center of Genomic medicine, Geneva, University Hospital of Geneva, SCV000897972.2

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

Description

This recessive variant was identified in a patient with repetitive pancreatitis. The patient harbours also a second variant (see above) in this gene in compound heterozygosity

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

From Sema4, Sema4, SCV002529711.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (17)

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

From MGZ Medical Genetics Center, SCV002580737.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Department of Molecular Genetics, Istishari Arab Hospital, SCV006297003.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The CFTR variant c.3154T>G creates an amino acid change from Phe to Val at position 1052. This variant has previously been reported in individuals with pancreatitis (PMID: 20460946, 17489851, 25704068, 25033378). It was detected with another heterozygous variant in the SPINK1 gene (c.-142T>C ). It is classified as pathogenic according to the recommendations of ACMG/AMP/ClinGen SVI guidelines. These two variants in the SPINK1 and CFTR genes has been described as a susceptibility factor contributing to pancreatitis, particularly when occurring together in a trans-heterozygous state. However, such variants are not sufficient on their own to cause disease, and are best interpreted in the context of a multifactorial etiology (PMID: 11938439, OMIM: 167800).

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

Last Updated: Jul 14, 2026

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