1-36466413-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000760.4(CSF3R):c.2455T>A(p.Phe819Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,348 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. F819L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000760.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.2455T>A | p.Phe819Ile | missense_variant | 17/17 | ENST00000373106.6 | NP_000751.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.2455T>A | p.Phe819Ile | missense_variant | 17/17 | 1 | NM_000760.4 | ENSP00000362198.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250136Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135326
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461348Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726958
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 02, 2024 | This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 819 of the CSF3R protein (p.Phe819Ile). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. 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. 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