rs398123047
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_001070.5(TUBG1):c.991A>C(p.Thr331Pro) variant causes a missense change. 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TUBG1
NM_001070.5 missense
NM_001070.5 missense
Scores
14
3
2
Clinical Significance
Conservation
PhyloP100: 7.19
Genes affected
TUBG1 (HGNC:12417): (tubulin gamma 1) This gene encodes a member of the tubulin superfamily. The encoded protein localizes to the centrosome where it binds to microtubules as part of a complex referred to as the gamma-tubulin ring complex. The protein mediates microtubule nucleation and is required for microtubule formation and progression of the cell cycle. A pseudogene of this gene is found on chromosome 7. [provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a helix (size 12) in uniprot entity TBG1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001070.5
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TUBG1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.928
PP5
?
Variant 17-42614407-A-C is Pathogenic according to our data. Variant chr17-42614407-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 65399.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBG1 | NM_001070.5 | c.991A>C | p.Thr331Pro | missense_variant | 9/11 | ENST00000251413.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBG1 | ENST00000251413.8 | c.991A>C | p.Thr331Pro | missense_variant | 9/11 | 1 | NM_001070.5 | 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:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at P330 (P = 0.0138);
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