rs11829764
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006009.4(TUBA1A):c.1008G>A(p.Lys336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,134 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 19 hom. )
Consequence
TUBA1A
NM_006009.4 synonymous
NM_006009.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.85
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 12-49185358-C-T is Benign according to our data. Variant chr12-49185358-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.85 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00792 (1207/152338) while in subpopulation AFR AF= 0.0264 (1099/41562). AF 95% confidence interval is 0.0251. There are 10 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1207 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.1008G>A | p.Lys336= | synonymous_variant | 4/4 | ENST00000301071.12 | |
TUBA1A | NM_001270399.2 | c.1008G>A | p.Lys336= | synonymous_variant | 4/4 | ||
TUBA1A | NM_001270400.2 | c.903G>A | p.Lys301= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.1008G>A | p.Lys336= | synonymous_variant | 4/4 | 1 | NM_006009.4 | P1 | |
TUBA1B-AS1 | ENST00000656133.1 | n.474-2925C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00786 AC: 1196AN: 152220Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00205 AC: 514AN: 250942Hom.: 7 AF XY: 0.00146 AC XY: 198AN XY: 135750
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GnomAD4 exome AF: 0.00108 AC: 1576AN: 1461796Hom.: 19 Cov.: 30 AF XY: 0.000916 AC XY: 666AN XY: 727206
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GnomAD4 genome ? AF: 0.00792 AC: 1207AN: 152338Hom.: 10 Cov.: 32 AF XY: 0.00714 AC XY: 532AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2015 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 24, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at