chr6-30724119-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5
The NM_178014.4(TUBB):c.1057G>A(p.Val353Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TUBB
NM_178014.4 missense
NM_178014.4 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 9.64
Genes affected
TUBB (HGNC:20778): (tubulin beta class I) This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TUBB
PP5
Variant 6-30724119-G-A is Pathogenic according to our data. Variant chr6-30724119-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 127190.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null. Variant chr6-30724119-G-A is described in UniProt as null.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB | NM_178014.4 | c.1057G>A | p.Val353Ile | missense_variant | 4/4 | ENST00000327892.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB | ENST00000327892.13 | c.1057G>A | p.Val353Ile | missense_variant | 4/4 | 1 | NM_178014.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 6 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 27, 2012 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpretted as Pathogenic and reported on 07-31-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MutPred
Gain of ubiquitination at K350 (P = 0.1375);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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