GeneBe

rs45476301

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001278552.2(TUBA4A):​c.-201C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TUBA4A
NM_001278552.2 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.883

Publications

1 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, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • autosomal dominant macrothrombocytopenia
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278552.2. 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+834G>C
intron
N/ANP_001342150.1Q9H853
TUBA4A
NM_001278552.2
c.-201C>G
5_prime_UTR
Exon 1 of 4NP_001265481.1P68366-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TUBA4B
ENST00000490341.3
TSL:2 MANE Select
c.12+834G>C
intron
N/AENSP00000487719.1Q9H853
TUBA4B
ENST00000473885.5
TSL:1
n.177+834G>C
intron
N/A
TUBA4B
ENST00000485041.5
TSL:1
n.177+834G>C
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
1
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
13
DANN
Benign
0.45
PhyloP100
0.88
PromoterAI
-0.18
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs45476301; hg19: chr2-220118975; API