chr10-47253-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_177987.3(TUBB8):c.1139G>A(p.Arg380His) 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 Uncertain significance (★★).
Frequency
Consequence
NM_177987.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 27
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461458Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727038
GnomAD4 genome Cov.: 27
ClinVar
Submissions by phenotype
Oocyte maturation defect 2 Pathogenic:1Uncertain:1
PM2_Supporting+PP2+PS4_Supporting+PP4 -
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not provided Uncertain:1
The p.Arg380His variant in TUBB8 has been reported in 6 individuals with oocyte maturation defects (Zhao 2020 PMID: 32524331, Zheng 2021 PMID: 33970371, Yang 2021 PMID:33009822). Additionally, this variant was identified through WGS analysis by the Broad Institute Rare Genomes Project in an adult female with infertility, parthenogenic activation of oocytes, and oocyte maturation defects and also in her mother with a history of infertility, fibroids, and recurrent miscarriage. It was absent from large population studies. This variant has also been reported in ClinVar (Variation ID 977679). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PS4, PM2_Supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at