rs1134868
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006009.4(TUBA1A):c.246C>T(p.Thr82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 149,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000045 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TUBA1A
NM_006009.4 synonymous
NM_006009.4 synonymous
Scores
1
3
10
Clinical Significance
Conservation
PhyloP100: -0.166
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00739038).
BP6
?
Variant 12-49186439-G-A is Benign according to our data. Variant chr12-49186439-G-A is described in ClinVar as [Benign]. Clinvar id is 212490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49186439-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.166 with no splicing effect.
BS2
?
High AC in GnomAd4 at 258 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA1A | NM_006009.4 | c.246C>T | p.Thr82= | synonymous_variant | 3/4 | ENST00000301071.12 | |
TUBA1A | NM_001270399.2 | c.246C>T | p.Thr82= | synonymous_variant | 3/4 | ||
TUBA1A | NM_001270400.2 | c.141C>T | p.Thr47= | synonymous_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA1A | ENST00000301071.12 | c.246C>T | p.Thr82= | synonymous_variant | 3/4 | 1 | NM_006009.4 | P1 | |
TUBA1B-AS1 | ENST00000656133.1 | n.474-1844G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00174 AC: 260AN: 149468Hom.: 0 Cov.: 30
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000446 AC: 65AN: 1458890Hom.: 0 Cov.: 46 AF XY: 0.0000372 AC XY: 27AN XY: 725930
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.00173 AC: 258AN: 149558Hom.: 0 Cov.: 30 AF XY: 0.00176 AC XY: 129AN XY: 73134
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 31, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
T
Vest4
MVP
ClinPred
T
GERP RS
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