rs11829764
Variant names:
Variant summary
Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006009.4(TUBA1A):c.1008G>A(p.Lys336Lys) 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
Publications
1 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 1207 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TUBA1A | NM_006009.4 | c.1008G>A | p.Lys336Lys | synonymous_variant | Exon 4 of 4 | ENST00000301071.12 | NP_006000.2 | |
| TUBA1A | NM_001270399.2 | c.1008G>A | p.Lys336Lys | synonymous_variant | Exon 4 of 4 | NP_001257328.1 | ||
| TUBA1A | NM_001270400.2 | c.903G>A | p.Lys301Lys | synonymous_variant | Exon 4 of 4 | NP_001257329.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00786 AC: 1196AN: 152220Hom.: 9 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1196
AN:
152220
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00205 AC: 514AN: 250942 AF XY: 0.00146 show subpopulations
GnomAD2 exomes
AF:
AC:
514
AN:
250942
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00108 AC: 1576AN: 1461796Hom.: 19 Cov.: 30 AF XY: 0.000916 AC XY: 666AN XY: 727206 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1576
AN:
1461796
Hom.:
Cov.:
30
AF XY:
AC XY:
666
AN XY:
727206
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
917
AN:
33454
American (AMR)
AF:
AC:
396
AN:
44688
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
7
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
3
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
105
AN:
1111988
Other (OTH)
AF:
AC:
148
AN:
60390
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.387
Heterozygous variant carriers
0
69
139
208
278
347
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00792 AC: 1207AN: 152338Hom.: 10 Cov.: 32 AF XY: 0.00714 AC XY: 532AN XY: 74494 show subpopulations
GnomAD4 genome
AF:
AC:
1207
AN:
152338
Hom.:
Cov.:
32
AF XY:
AC XY:
532
AN XY:
74494
show subpopulations
African (AFR)
AF:
AC:
1099
AN:
41562
American (AMR)
AF:
AC:
82
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
11
AN:
68038
Other (OTH)
AF:
AC:
14
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
62
124
187
249
311
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
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
May 05, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Apr 12, 2016
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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. -
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:2
Jun 24, 2019
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.