rs551466727
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM1PP2BP4_ModerateBS2
The ENST00000251849.9(RAF1):c.997C>T(p.Arg333Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,612,302 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. R333G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000251849.9 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAF1 | NM_002880.4 | c.997C>T | p.Arg333Cys | missense_variant | 10/17 | ENST00000251849.9 | NP_002871.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAF1 | ENST00000251849.9 | c.997C>T | p.Arg333Cys | missense_variant | 10/17 | 1 | NM_002880.4 | ENSP00000251849 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460060Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 726512
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Dec 18, 2018 | - - |
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 333 of the RAF1 protein (p.Arg333Cys). This variant is present in population databases (rs551466727, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 411094). 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 RAF1 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