11-119206442-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005188.4(CBL):āc.25T>Cā(p.Ser9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,425,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S9F) has been classified as Uncertain significance.
Frequency
Consequence
NM_005188.4 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 |
---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | c.25T>C | p.Ser9Pro | missense_variant | 1/16 | ENST00000264033.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBL | ENST00000264033.6 | c.25T>C | p.Ser9Pro | missense_variant | 1/16 | 1 | NM_005188.4 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000104 AC: 2AN: 192646Hom.: 0 AF XY: 0.00000950 AC XY: 1AN XY: 105310
GnomAD4 exome AF: 0.00000281 AC: 4AN: 1425924Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1AN XY: 706728
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2021 | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt CBL protein function. This variant has not been reported in the literature in individuals affected with CBL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 9 of the CBL protein (p.Ser9Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at