rs1555162325
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_006009.4(TUBA1A):c.920C>T(p.Pro307Leu) 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 Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P307S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006009.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.920C>T | p.Pro307Leu | missense_variant | 4/4 | ENST00000301071.12 | NP_006000.2 | |
TUBA1A | NM_001270399.2 | c.920C>T | p.Pro307Leu | missense_variant | 4/4 | NP_001257328.1 | ||
TUBA1A | NM_001270400.2 | c.815C>T | p.Pro272Leu | missense_variant | 4/4 | NP_001257329.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.920C>T | p.Pro307Leu | missense_variant | 4/4 | 1 | NM_006009.4 | ENSP00000301071.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lissencephaly due to TUBA1A mutation Pathogenic:1
Likely pathogenic, 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 - |
Tubulinopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | literature only | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Jul 01, 2018 | A variant that is classified as pathogenic has been identified in the TUBA1A gene in a born individual of male sex. The c.920C>T, p.(Pro307Leu) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Wiszniewski et al. Eur J Hum Genet, 2018 PMID: 29706646. HPO-standardized clinical features were: Hypoplasia of the corpus callosum (HP:0002079); Cerebellar vermis hypoplasia (HP:0001320); Cerebellar hypoplasia (HP:0001321); Gray matter heterotopia (HP:0002281); Generalized tonic-clonic seizures (HP:0002069) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at