rs868444265
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000631.5(NCF4):c.388C>T(p.Arg130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,894 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 (★). Synonymous variant affecting the same amino acid position (i.e. R130R) has been classified as Likely benign.
Frequency
Consequence
NM_000631.5 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.388C>T | p.Arg130Trp | missense_variant | 5/10 | ENST00000248899.11 | NP_000622.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.388C>T | p.Arg130Trp | missense_variant | 5/10 | 1 | NM_000631.5 | ENSP00000248899.6 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251284Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135818
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461740Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727156
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 130 of the NCF4 protein (p.Arg130Trp). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NCF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 570297). 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