7-117534349-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The ENST00000003084.11(CFTR):āc.563T>Cā(p.Leu188Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L188M) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000003084.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.563T>C | p.Leu188Pro | missense_variant | 5/27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.563T>C | p.Leu188Pro | missense_variant | 5/27 | 1 | NM_000492.4 | ENSP00000003084 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250382Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135436
GnomAD4 exome AF: 7.08e-7 AC: 1AN: 1412420Hom.: 0 Cov.: 24 AF XY: 0.00000142 AC XY: 1AN XY: 705734
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 08, 2024 | Variant summary: CFTR c.563T>C (p.Leu188Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250382 control chromosomes. c.563T>C has been reported in the literature in individuals affected with Idiopathic Chronic Pancreatitis and CFTR-related Metabolic alkalosis/failure to thrive/hypokalemia (example, Audrezet_2008, Hamoir_2013, Masson_2013, Sinha_2022). Particularly, it has been reported at a compound heterozygous state with two different pathogenic nonsense variants in CFTR in three unrelated cases (Hamoir_2013, Masson_2013, Sinha_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18687795, 23751316, 23951356, 35006361). ClinVar contains an entry for this variant (Variation ID: 551100, VUS). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Cystic fibrosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 24, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at