chr16-88643375-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000101.4(CYBA):c.566C>T(p.Pro189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,530,724 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. P189R) has been classified as Likely benign.
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.566C>T | p.Pro189Leu | missense_variant | 6/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.*1791C>T | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.566C>T | p.Pro189Leu | missense_variant | 6/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000166 AC: 2AN: 120168Hom.: 0 AF XY: 0.0000150 AC XY: 1AN XY: 66502
GnomAD4 exome AF: 0.0000276 AC: 38AN: 1378640Hom.: 0 Cov.: 32 AF XY: 0.0000324 AC XY: 22AN XY: 679776
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74296
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.566C>T (p.P189L) alteration is located in exon 6 (coding exon 6) of the CYBA gene. This alteration results from a C to T substitution at nucleotide position 566, causing the proline (P) at amino acid position 189 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 189 of the CYBA protein (p.Pro189Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: "Possibly 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