16-88646773-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_000101.4(CYBA):c.269G>A(p.Arg90Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,700 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.269G>A | p.Arg90Gln | missense_variant | 4/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.269G>A | p.Arg90Gln | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.269G>A | p.Arg90Gln | missense_variant | 4/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251050Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727174
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 90 of the CYBA protein (p.Arg90Gln). This variant is present in population databases (rs104894513, gnomAD 0.003%). This missense change has been observed in individual(s) with chronic granulomatous disease (PMID: 2243141, 29560547, 30470980). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G-297>A (Arg-90>Gln). ClinVar contains an entry for this variant (Variation ID: 2258). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg90 amino acid residue in CYBA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10910929, 20167518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1992 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at