rs17725343
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_014444.5(TUBGCP4):c.*4110C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 587,522 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.019 ( 52 hom., cov: 32)
Exomes 𝑓: 0.023 ( 182 hom. )
Consequence
TUBGCP4
NM_014444.5 3_prime_UTR
NM_014444.5 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.23
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]
TP53BP1 (HGNC:11999): (tumor protein p53 binding protein 1) This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0194 (2955/152338) while in subpopulation NFE AF= 0.0273 (1855/68036). AF 95% confidence interval is 0.0262. There are 52 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 52 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP4 | NM_014444.5 | c.*4110C>T | 3_prime_UTR_variant | 18/18 | ENST00000564079.6 | ||
TP53BP1 | NM_001141980.3 | c.5401-228G>A | intron_variant | ENST00000382044.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP4 | ENST00000564079.6 | c.*4110C>T | 3_prime_UTR_variant | 18/18 | 1 | NM_014444.5 | A1 | ||
TP53BP1 | ENST00000382044.9 | c.5401-228G>A | intron_variant | 1 | NM_001141980.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0194 AC: 2955AN: 152220Hom.: 52 Cov.: 32
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GnomAD4 exome AF: 0.0233 AC: 10145AN: 435184Hom.: 182 Cov.: 4 AF XY: 0.0234 AC XY: 5347AN XY: 228304
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GnomAD4 genome ? AF: 0.0194 AC: 2955AN: 152338Hom.: 52 Cov.: 32 AF XY: 0.0190 AC XY: 1418AN XY: 74494
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at