rs1555436162
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_052903.6(TUBGCP5):c.2180T>G(p.Phe727Cys) variant causes a missense change involving the alteration of a 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TUBGCP5
NM_052903.6 missense
NM_052903.6 missense
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 8.46
Genes affected
TUBGCP5 (HGNC:18600): (tubulin gamma complex component 5) Enables microtubule binding activity. Involved in microtubule nucleation. Located in centrosome and cytosol. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]
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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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.887
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP5 | NM_052903.6 | c.2180T>G | p.Phe727Cys | missense_variant | 16/23 | ENST00000615383.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP5 | ENST00000615383.5 | c.2180T>G | p.Phe727Cys | missense_variant | 16/23 | 1 | NM_052903.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Microcephaly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Apr 10, 2018 | We report a novel homozygous missense mutation in the TUBGCP5 gene (tubulin gamma complex associated protein 5) in a patient with microcephaly and mild developmental delay. This is a rare homozygous missense variant in the TUBGCP5 gene (c.2180T>G) in the patient, causing an amino-acid substitution of phenylalanine to cysteine at position 727 of the protein (TUBGCP5:p.Phe727Cys). This position is extremely conserved, as shown by population allele frequency data from ExAC and GnomAD, as well as comparisons with all other vertebrates. Furthermore, several of the known genes associated with MCPH are involved in the formation and function of the centrosome, including two paralogs of TUBGCP5; TUBGCP4 and TUBGCP6, also supporting our hypothesis. The identified recessive homozygous missense mutation in TUBGCP5 may thus represent a novel cause of MCPH with mild developmental delay. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
LIST_S2
Uncertain
D;D
MetaRNN
Pathogenic
D;D
Sift4G
Uncertain
D;D
Vest4
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