rs397508220
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_000492.4(CFTR):c.149C>A(p.Ser50Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000253 in 1,581,314 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S50P) has been classified as Pathogenic.
Frequency
Consequence
NM_000492.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.149C>A | p.Ser50Tyr | missense_variant | 2/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.149C>A | p.Ser50Tyr | missense_variant | 2/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000210 AC: 3AN: 1429280Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 713242
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74232
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:3Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 08, 2024 | The p.S50Y variant (also known as c.149C>A), located in coding exon 2 of the CFTR gene, results from a C to A substitution at nucleotide position 149. The serine at codon 50 is replaced by tyrosine, an amino acid with dissimilar properties. This alteration was described in an individual with congenital bilateral absence of the vas deferens (CBAVD), who was reported to also carry deltaF508 in trans (Zielenski J et al. Hum. Mutat., 1997;9:183-4). Of note, this alteration is also designated as 281C>A in published literature. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 03, 2017 | - - |
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 14, 2024 | Variant summary: Variant summary: The CPT2 c.149C>A (p.Pro50His) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a damaging outcome. This variant was found in 2/11728 control chromosomes at a frequency of 0.0001705, which does not exceed the estimated maximal expected allele frequency of a pathogenic CPT2 variant (0.0015811). Multiple publications cite the variant in compound heterozygote affected individuals, which were found to have low CPT II activity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. - |
CFTR-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 27, 2019 | - - |
Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at