rs1555394750
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014444.5(TUBGCP4):c.914A>C(p.Asp305Ala) 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 29)
Consequence
TUBGCP4
NM_014444.5 missense
NM_014444.5 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 9.00
Genes affected
TUBGCP4 (HGNC:16691): (tubulin gamma complex component 4) This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP4 | NM_014444.5 | c.914A>C | p.Asp305Ala | missense_variant | 9/18 | ENST00000564079.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP4 | ENST00000564079.6 | c.914A>C | p.Asp305Ala | missense_variant | 9/18 | 1 | NM_014444.5 | A1 | |
TUBGCP4 | ENST00000260383.11 | c.914A>C | p.Asp305Ala | missense_variant | 9/18 | 1 | P4 | ||
TUBGCP4 | ENST00000561691.5 | c.671A>C | p.Asp224Ala | missense_variant, NMD_transcript_variant | 7/17 | 1 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD3 genomes
Cov.:
29
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 29
GnomAD4 genome
Cov.:
29
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 23, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
MPC
1.1
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