12-49185063-CCTCCTCATAATCCTT-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM4PP3PP5_Moderate
The NM_006009.4(TUBA1A):c.1288_1302delAAGGATTATGAGGAG(p.Lys430_Glu434del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TUBA1A
NM_006009.4 conservative_inframe_deletion
NM_006009.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.87
Genes affected
TUBA1A (HGNC:20766): (tubulin alpha 1a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to the mouse and rat Tuba1 genes. Northern blot studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q. Mutations in this gene cause lissencephaly type 3 (LIS3) - a neurological condition characterized by microcephaly, intellectual disability, and early-onset epilepsy caused by defective neuronal migration. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
In a helix (size 17) in uniprot entity TBA1A_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_006009.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_006009.4.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 12-49185063-CCTCCTCATAATCCTT-C is Pathogenic according to our data. Variant chr12-49185063-CCTCCTCATAATCCTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 1065497.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.1288_1302delAAGGATTATGAGGAG | p.Lys430_Glu434del | conservative_inframe_deletion | 4/4 | ENST00000301071.12 | NP_006000.2 | |
TUBA1A | NM_001270399.2 | c.1288_1302delAAGGATTATGAGGAG | p.Lys430_Glu434del | conservative_inframe_deletion | 4/4 | NP_001257328.1 | ||
TUBA1A | NM_001270400.2 | c.1183_1197delAAGGATTATGAGGAG | p.Lys395_Glu399del | conservative_inframe_deletion | 4/4 | NP_001257329.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.1288_1302delAAGGATTATGAGGAG | p.Lys430_Glu434del | conservative_inframe_deletion | 4/4 | 1 | NM_006009.4 | ENSP00000301071.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lissencephaly due to TUBA1A mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Medicine Lab, University of California San Francisco | Sep 26, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.