rs34362628
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000760.4(CSF3R):c.101C>T(p.Pro34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,607,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.101C>T | p.Pro34Leu | missense_variant | 4/17 | ENST00000373106.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.101C>T | p.Pro34Leu | missense_variant | 4/17 | 1 | NM_000760.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152078Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249994Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135096
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1454830Hom.: 1 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 722184
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152196Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74392
ClinVar
Submissions by phenotype
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 34 of the CSF3R protein (p.Pro34Leu). This variant is present in population databases (rs34362628, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. ClinVar contains an entry for this variant (Variation ID: 567052). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CSF3R protein function. 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