Variant NM_000492.4:c.1675G>A


Variant details:
Name NM_000492.4:c.1675G>A
Protein name NP_000483.3:p.(Ala559Thr)
Genomic name (hg19) chr7:g.117227883G>A    UCSC    gnomAD
#Exon/intron exon 12
Legacy Name A559T
Class disease-causing
Subclass CF-causing
WT sequence AGGTCAACGAGCAAGAATTTCTTTA G CAAGGTGAATAACTAATTATTGGTC
Mutant sequence AGGTCAACGAGCAAGAATTTCTTTA A CAAGGTGAATAACTAATTATTGGTC


External sources:
dbSNP
rs75549581


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Gregory et al, 1991 1712898 ✓ ✓
Van Goor et al, 2014 23891399 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓


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




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


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

TOTAL NUMBER OF PATIENTS 4
CF 2
Pending (NBS) 2



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Pending (NBS) 1064heterozygotevarying clinical consequence - Trans
Pending (NBS) 5881heterozygoteCF-causing- Undef
CF 3545heterozygoteCF-causing - Trans
CF 4230heterozygoteCF-causing - Trans
VUS2 - 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.