12-49185913-C-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006009.4(TUBA1A):āc.453G>Cā(p.Ser151Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,612,662 control chromosomes in the GnomAD database, including 126,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.45 ( 17126 hom., cov: 30)
Exomes š: 0.38 ( 108876 hom. )
Consequence
TUBA1A
NM_006009.4 synonymous
NM_006009.4 synonymous
Scores
1
13
Clinical Significance
Conservation
PhyloP100: 0.300
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=1.1844239E-5).
BP6
Variant 12-49185913-C-G is Benign according to our data. Variant chr12-49185913-C-G is described in ClinVar as [Benign]. Clinvar id is 160157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49185913-C-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.3 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.453G>C | p.Ser151Ser | synonymous_variant | 4/4 | ENST00000301071.12 | NP_006000.2 | |
TUBA1A | NM_001270399.2 | c.453G>C | p.Ser151Ser | synonymous_variant | 4/4 | NP_001257328.1 | ||
TUBA1A | NM_001270400.2 | c.348G>C | p.Ser116Ser | synonymous_variant | 4/4 | NP_001257329.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.453G>C | p.Ser151Ser | synonymous_variant | 4/4 | 1 | NM_006009.4 | ENSP00000301071.7 |
Frequencies
GnomAD3 genomes AF: 0.453 AC: 68608AN: 151586Hom.: 17079 Cov.: 30
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GnomAD3 exomes AF: 0.416 AC: 104302AN: 250668Hom.: 23555 AF XY: 0.416 AC XY: 56424AN XY: 135530
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GnomAD4 exome AF: 0.377 AC: 550350AN: 1460954Hom.: 108876 Cov.: 76 AF XY: 0.379 AC XY: 275721AN XY: 726792
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GnomAD4 genome AF: 0.453 AC: 68717AN: 151708Hom.: 17126 Cov.: 30 AF XY: 0.457 AC XY: 33894AN XY: 74092
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Lissencephaly due to TUBA1A mutation Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
TUBA1A-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 28, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Vest4
ClinPred
T
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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