NM_006009.4:c.1256C>T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM1PM2PP2PP3PP5_Very_Strong
The NM_006009.4(TUBA1A):c.1256C>T(p.Ser419Leu) 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 (★★).
Frequency
Consequence
NM_006009.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.1256C>T | p.Ser419Leu | missense_variant | Exon 4 of 4 | ENST00000301071.12 | NP_006000.2 | |
TUBA1A | NM_001270399.2 | c.1256C>T | p.Ser419Leu | missense_variant | Exon 4 of 4 | NP_001257328.1 | ||
TUBA1A | NM_001270400.2 | c.1151C>T | p.Ser384Leu | missense_variant | Exon 4 of 4 | NP_001257329.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lissencephaly due to TUBA1A mutation Pathogenic:2
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This variant was identified as de novo mosaic (maternity and paternity confirmed)._x000D_ Criteria applied: PS2, PS4_MOD, PM1, PM2_SUP, PP3 -
not provided Pathogenic:1
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Tubulinopathy Pathogenic:1
A variant that is classified as pathogenic has been identified in the TUBA1A gene in a 2 years old born individual of male sex. The c.1256C>T, p.(Ser419Leu) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Poirier et al. Hum Mutat, 2007 PMID: 17584854. HPO-standardized clinical features were: Dysplastic corpus callosum (HP:0006989); Pachygyria (HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); no Abnormality of brainstem morphology (-HP:0002363); Dysgenesis of the hippocampus (HP:0025101); Dilation of lateral ventricles (HP:0006956); Gray matter heterotopia (HP:0002281); no Congenital microcephaly (-HP:0011451); no Microcephaly (-HP:0000252); Spasticity (HP:0001257); Generalized tonic-clonic seizures (HP:0002069) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at