rs104894515
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_000101.4(CYBA):c.467C>T(p.Pro156Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000653 in 1,532,140 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. P156Q) has been classified as Pathogenic.
Frequency
Consequence
NM_000101.4 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 | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.467C>T | p.Pro156Leu | missense_variant | 6/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.*1692C>T | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.467C>T | p.Pro156Leu | missense_variant | 6/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000580 AC: 8AN: 1379934Hom.: 0 Cov.: 37 AF XY: 0.00000881 AC XY: 6AN XY: 680896
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74406
ClinVar
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 156 of the CYBA protein (p.Pro156Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CYBA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at