GeneBe

rs3051654

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001355221.1(TUBA4B):​c.12+536_12+541delGGGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 382,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

TUBA4B
NM_001355221.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.757

Publications

0 publications found
Variant links:
Genes affected
TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]
TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of 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 and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
TUBA4A Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis type 22
    Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
  • autosomal dominant macrothrombocytopenia
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355221.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TUBA4B
NM_001355221.1
MANE Select
c.12+536_12+541delGGGGGG
intron
N/ANP_001342150.1Q9H853
TUBA4A
NM_001278552.2
c.-43+139_-43+144delCCCCCC
intron
N/ANP_001265481.1P68366-2
TUBA4A
NM_006000.3
MANE Select
c.-98_-93delCCCCCC
upstream_gene
N/ANP_005991.1P68366-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TUBA4B
ENST00000490341.3
TSL:2 MANE Select
c.12+532_12+537delGGGGGG
intron
N/AENSP00000487719.1Q9H853
TUBA4B
ENST00000473885.5
TSL:1
n.177+532_177+537delGGGGGG
intron
N/A
TUBA4B
ENST00000485041.5
TSL:1
n.177+532_177+537delGGGGGG
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000261
AC:
1
AN:
382862
Hom.:
0
AF XY:
0.00000536
AC XY:
1
AN XY:
186730
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
11792
American (AMR)
AF:
0.00
AC:
0
AN:
5398
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
7454
East Asian (EAS)
AF:
0.00
AC:
0
AN:
17654
South Asian (SAS)
AF:
0.00
AC:
0
AN:
9512
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23518
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1324
European-Non Finnish (NFE)
AF:
0.00000347
AC:
1
AN:
288314
Other (OTH)
AF:
0.00
AC:
0
AN:
17896
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
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
75-80
>80
Age
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3051654; hg19: chr2-220118672; API