chr2-219250485-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_006000.3(TUBA4A):c.1214T>G(p.Val405Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
TUBA4A
NM_006000.3 missense
NM_006000.3 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 9.29
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TUBA4A
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.8
BS2
?
High AC in GnomAdExome at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA4A | NM_006000.3 | c.1214T>G | p.Val405Gly | missense_variant | 4/4 | ENST00000248437.9 | |
TUBA4A | NM_001278552.2 | c.1169T>G | p.Val390Gly | missense_variant | 4/4 | ||
TUBA4A | XM_047445674.1 | c.1241T>G | p.Val414Gly | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA4A | ENST00000248437.9 | c.1214T>G | p.Val405Gly | missense_variant | 4/4 | 1 | NM_006000.3 | P1 | |
TUBA4A | ENST00000392088.6 | c.1169T>G | p.Val390Gly | missense_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251488Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135922
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727236
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
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ExAC
?
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7
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust | Jan 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift4G
Pathogenic
D;D
Polyphen
B;.
Vest4
MutPred
Loss of stability (P = 0.0179);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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