Variant NM_000492.4:c.3199G>A


Variant details:
Name NM_000492.4:c.3199G>A
Protein name NP_000483.3:p.(Ala1067Thr)
Genomic name (hg19) chr7:g.117251694G>A    UCSC    gnomAD
#Exon/intron exon 20
Legacy Name A1067T
Class VUS
Subclass VUS2
WT sequence CTTAAAAGGACTATGGACACTTCGT G CCTTCGGACGGCAGCCTTACTTTGA
Mutant sequence CTTAAAAGGACTATGGACACTTCGT A CCTTCGGACGGCAGCCTTACTTTGA


External sources:

Not found		dbSNP
rs121909020


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Seibert et al, 1996 8662892 ✓ ✓
Cotten et al, 1996 8702904 ✓ ✓
Van Goor et al, 2014 23891399 ✓ ✓ ✓


« ✓ » indicates the type of analysis performed and not the results


Response to modulators:


Modulator FDA approval EMA approval in vitro / ex vivo data clinical data
IVA yesnoyesno
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C55 1e-05 0 1
VUS5 VUS5 VUS5 VUS5

Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing




No patient found in CFTR-NGS catalogue


3 patients carrying this variant are reported in CFTR-France:

TOTAL NUMBER OF PATIENTS 3
CFTR-RD2
  • CBAVD  2
Fetal bowel anomalies 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 391heterozygoteCF-causing - Cis
CFTR-RD-causing - Trans
CBAVD 1421heterozygoteCFTR-RD-causing- Undef
CF-causing- Undef
Fetal bowel anomalies 5357heterozygoteCF-causing - Cis
VUS3 - Trans


Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing



            CFTR variants are clustered into five groups:
  • CF-causing: when in trans with another CF-causing mutation, will result in CF.
  • CFTR-RD causing: when in trans with a CF-causing mutation, will result in CFTR-related disorders (CFTR-RD) such as chronic pancreatitis, bronchiectasis, CRS-NP (chronic rhinosinusitis with or without nasal polyposis) or CBAVD (congenital absence of vas deferens), according to Bombieri C et al., 2011.
  • Varying clinical consequence: when in trans with another CF-causing mutation, can either result in CF or in a CFTR-RD.
  • Non disease-causing: when in trans with a CF-causing mutation, will not cause CF, nor CFTR-RD.
  • VUS (Variant of unknown clinical significance): unclassified because of insufficient data.