12-49185142-G-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006009.4(TUBA1A):c.1224C>A(p.Tyr408Ter) variant causes a stop gained change involving the alteration of a non-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). Synonymous variant affecting the same amino acid position (i.e. Y408Y) has been classified as Likely benign.
Frequency
Consequence
NM_006009.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.1224C>A | p.Tyr408Ter | stop_gained | 4/4 | ENST00000301071.12 | |
TUBA1A | NM_001270399.2 | c.1224C>A | p.Tyr408Ter | stop_gained | 4/4 | ||
TUBA1A | NM_001270400.2 | c.1119C>A | p.Tyr373Ter | stop_gained | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.1224C>A | p.Tyr408Ter | stop_gained | 4/4 | 1 | NM_006009.4 | P1 | |
TUBA1B-AS1 | ENST00000656133.1 | n.474-3141G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lissencephaly due to TUBA1A mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 10, 2013 | This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in a 20-year-old male with bilateral perisylvian polymicrogyria, epilepsy, abnormal gait, global delays - |
Tubulinopathy Uncertain:1
Uncertain significance, 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 VUS has been identified in the TUBA1A gene in a born individual of unknown sex. The c.1224C>A, p.(Tyr408*) variant has been reported as a variant of germline/unknown origin. This variant and associated phenotype was previously reported by Posey et al. Genet Med, 2016 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at