16-88643367-C-G
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000101.4(CYBA):c.574G>C(p.Asp192His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,526,540 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. D192N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
Publications
- granulomatous disease, chronic, autosomal recessive, cytochrome b-negativeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- chronic granulomatous diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000824 AC: 1AN: 121396 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 7.28e-7 AC: 1AN: 1374476Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 677672 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74268 show subpopulations
ClinVar
Submissions by phenotype
Chronic granulomatous disease Uncertain:1
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Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 192 of the CYBA protein (p.Asp192His). 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. ClinVar contains an entry for this variant (Variation ID: 948436). 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