6-30722980-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5
The NM_178014.4(TUBB):c.229C>T(p.Arg77Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TUBB
NM_178014.4 missense
NM_178014.4 missense
Scores
8
6
3
Clinical Significance
Conservation
PhyloP100: 3.32
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TUBB
PP3
MetaRNN computational evidence supports a deleterious effect, 0.933
PP5
Variant 6-30722980-C-T is Pathogenic according to our data. Variant chr6-30722980-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 985795.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB | NM_178014.4 | c.229C>T | p.Arg77Cys | missense_variant | 3/4 | ENST00000327892.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB | ENST00000327892.13 | c.229C>T | p.Arg77Cys | missense_variant | 3/4 | 1 | NM_178014.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | TUBB: PS2, PM2, PP2, PP3 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0101);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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