rs281860279
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001288705.3(CSF1R):c.2624T>C(p.Met875Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001288705.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSF1R | ENST00000675795.1 | c.2624T>C | p.Met875Thr | missense_variant | Exon 19 of 21 | NM_001288705.3 | ENSP00000501699.1 | |||
CSF1R | ENST00000286301.7 | c.2624T>C | p.Met875Thr | missense_variant | Exon 20 of 22 | 1 | ENSP00000286301.3 | |||
CSF1R | ENST00000504875.5 | n.*445T>C | non_coding_transcript_exon_variant | Exon 18 of 20 | 1 | ENSP00000422212.1 | ||||
CSF1R | ENST00000504875.5 | n.*445T>C | 3_prime_UTR_variant | Exon 18 of 20 | 1 | ENSP00000422212.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary diffuse leukoencephalopathy with spheroids Pathogenic:1
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not provided Pathogenic:1
This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 875 of the CSF1R protein (p.Met875Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of hereditary diffuse leukoencephalopathy with spheroids (PMID: 22197934; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 29810). Invitae Evidence 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 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 CSF1R protein function. Experimental studies have shown that this missense change affects CSF1R function (PMID: 22197934, 23408870, 24120500, 24145216, 24336230). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at