rs1555162323
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The NM_006009.4(TUBA1A):c.959G>A(p.Arg320His) 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. R320C) 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 | UniProt |
---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.959G>A | p.Arg320His | missense_variant | 4/4 | ENST00000301071.12 | |
TUBA1A | NM_001270399.2 | c.959G>A | p.Arg320His | missense_variant | 4/4 | ||
TUBA1A | NM_001270400.2 | c.854G>A | p.Arg285His | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.959G>A | p.Arg320His | missense_variant | 4/4 | 1 | NM_006009.4 | P1 | |
TUBA1B-AS1 | ENST00000656133.1 | n.474-2876C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2017 | - - |
Lissencephaly due to TUBA1A mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues | Jul 05, 2022 | - - |
TUBA1A-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 15, 2023 | The TUBA1A c.959G>A variant is predicted to result in the amino acid substitution p.Arg320His. This variant has been reported as a de novo variant in multiple individuals with lissencephaly (see for example, Table 1, Bahi-Buisson et al. 2014. PubMed ID: 24860126; Table 1, Lefebvre et al. 2020. PubMed ID: 32732226; Table 1, Weber et al. 2022. PubMed ID: 35686685). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. - |
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 25 gestational week old fetal individual of male sex. The c.959G>A, p.(Arg320His) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Bahi-Buisson et al. Brain, 2014 PMID: 24860126. HPO-standardized clinical features were: Partial agenesis of the corpus callosum (HP:0001338); Agyria (HP:0031882); Dysgenesis of the cerebellar vermis (HP:0002195); Hypoplasia of the brainstem (HP:0002365); Cerebellar dysplasia (HP:0007033); Gray matter heterotopia (HP:0002281); Microcephaly (HP:0000252) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at