chr22-36861193-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000631.5(NCF4):c.22C>T(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,551,368 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R8Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000631.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.22C>T | p.Arg8Trp | missense_variant | 1/10 | ENST00000248899.11 | |
NCF4-AS1 | NR_147197.1 | n.351+8900G>A | intron_variant, non_coding_transcript_variant | ||||
NCF4 | NM_013416.4 | c.22C>T | p.Arg8Trp | missense_variant | 1/9 | ||
NCF4 | XM_047441385.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.22C>T | p.Arg8Trp | missense_variant | 1/10 | 1 | NM_000631.5 | P1 | |
NCF4-AS1 | ENST00000619915.1 | n.349+8900G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000195 AC: 3AN: 153454Hom.: 0 AF XY: 0.0000246 AC XY: 2AN XY: 81360
GnomAD4 exome AF: 0.00000929 AC: 13AN: 1399146Hom.: 0 Cov.: 31 AF XY: 0.00000869 AC XY: 6AN XY: 690092
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2020 | 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. 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"). This variant has not been reported in the literature in individuals with NCF4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 8 of the NCF4 protein (p.Arg8Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at