chr6-30723922-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3_ModeratePP5
The NM_178014.4(TUBB):c.860C>T(p.Pro287Leu) 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P287S) has been classified as Pathogenic.
Frequency
Consequence
NM_178014.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB | NM_178014.4 | c.860C>T | p.Pro287Leu | missense_variant | 4/4 | ENST00000327892.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB | ENST00000327892.13 | c.860C>T | p.Pro287Leu | missense_variant | 4/4 | 1 | NM_178014.4 | P1 | |
ENST00000607476.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 6 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Sep 01, 2017 | this variant was indentified in an individual with malformations of cortical development - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 12, 2022 | - - |
Multiple benign circumferential skin creases on limbs 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 12, 2022 | - - |
Lissencephaly Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2018 | The P287L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P287L variant is not observed in large population cohorts (Lek et al., 2016). The P287L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret P287L as a likely pathogenic variant. - |
Seizure Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Nov 23, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at