rs765483435
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6
The NM_006009.4(TUBA1A):c.273A>G(p.Gln91Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000023 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TUBA1A
NM_006009.4 synonymous
NM_006009.4 synonymous
Scores
1
1
13
Clinical Significance
Conservation
PhyloP100: 3.21
Publications
2 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: Likely_benign. The variant received -1 ACMG points.
BP6
Variant 12-49186412-T-C is Benign according to our data. Variant chr12-49186412-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212492.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006009.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TUBA1A | NM_006009.4 | MANE Select | c.273A>G | p.Gln91Gln | synonymous | Exon 3 of 4 | NP_006000.2 | ||
| TUBA1A | NM_001270399.2 | c.273A>G | p.Gln91Gln | synonymous | Exon 3 of 4 | NP_001257328.1 | |||
| TUBA1A | NM_001270400.2 | c.168A>G | p.Gln56Gln | synonymous | Exon 3 of 4 | NP_001257329.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TUBA1A | ENST00000301071.12 | TSL:1 MANE Select | c.273A>G | p.Gln91Gln | synonymous | Exon 3 of 4 | ENSP00000301071.7 | ||
| TUBA1A | ENST00000550767.6 | TSL:1 | c.168A>G | p.Gln56Gln | synonymous | Exon 4 of 5 | ENSP00000446637.1 | ||
| TUBA1A | ENST00000546918.1 | TSL:3 | c.425A>G | p.Asn142Ser | missense | Exon 2 of 3 | ENSP00000446613.1 |
Frequencies
GnomAD3 genomes AF: 0.000569 AC: 85AN: 149280Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
85
AN:
149280
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000800 AC: 2AN: 249848 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
249848
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000234 AC: 34AN: 1450206Hom.: 0 Cov.: 46 AF XY: 0.0000236 AC XY: 17AN XY: 721540 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
34
AN:
1450206
Hom.:
Cov.:
46
AF XY:
AC XY:
17
AN XY:
721540
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33358
American (AMR)
AF:
AC:
5
AN:
43678
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25692
East Asian (EAS)
AF:
AC:
4
AN:
38078
South Asian (SAS)
AF:
AC:
3
AN:
85634
European-Finnish (FIN)
AF:
AC:
8
AN:
50944
Middle Eastern (MID)
AF:
AC:
2
AN:
5582
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1107402
Other (OTH)
AF:
AC:
2
AN:
59838
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.260
Heterozygous variant carriers
0
6
12
19
25
31
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000569 AC: 85AN: 149378Hom.: 0 Cov.: 30 AF XY: 0.000741 AC XY: 54AN XY: 72884 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
85
AN:
149378
Hom.:
Cov.:
30
AF XY:
AC XY:
54
AN XY:
72884
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
7
AN:
41146
American (AMR)
AF:
AC:
10
AN:
14760
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
3370
East Asian (EAS)
AF:
AC:
4
AN:
5020
South Asian (SAS)
AF:
AC:
1
AN:
4760
European-Finnish (FIN)
AF:
AC:
27
AN:
10006
Middle Eastern (MID)
AF:
AC:
0
AN:
284
European-Non Finnish (NFE)
AF:
AC:
30
AN:
67118
Other (OTH)
AF:
AC:
4
AN:
2058
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.241
Heterozygous variant carriers
0
14
28
43
57
71
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
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55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ExAC
AF:
AC:
109
ClinVar
ClinVar submissions as Germline
Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
-
2
not provided (2)
-
1
-
not specified (1)
-
-
1
TUBA1A-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
PhyloP100
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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