chr22-36861194-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000631.5(NCF4):c.23G>A(p.Arg8Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000413 in 1,551,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R8W) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.23G>A | p.Arg8Gln | missense_variant | 1/10 | ENST00000248899.11 | |
NCF4-AS1 | NR_147197.1 | n.351+8899C>T | intron_variant, non_coding_transcript_variant | ||||
NCF4 | NM_013416.4 | c.23G>A | p.Arg8Gln | 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.23G>A | p.Arg8Gln | missense_variant | 1/10 | 1 | NM_000631.5 | P1 | |
NCF4-AS1 | ENST00000619915.1 | n.349+8899C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000521 AC: 8AN: 153414Hom.: 0 AF XY: 0.0000738 AC XY: 6AN XY: 81332
GnomAD4 exome AF: 0.0000400 AC: 56AN: 1399142Hom.: 0 Cov.: 31 AF XY: 0.0000420 AC XY: 29AN XY: 690092
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74492
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 | May 15, 2023 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1499091). This variant has not been reported in the literature in individuals affected with NCF4-related conditions. This variant is present in population databases (rs762576326, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 8 of the NCF4 protein (p.Arg8Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at