rs869025612
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3PP5_Moderate
The NM_177987.3(TUBB8):c.900G>A(p.Met300Ile) 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 (★).
Frequency
Genomes: not found (cov: 29)
Consequence
TUBB8
NM_177987.3 missense
NM_177987.3 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 5.57
Genes affected
TUBB8 (HGNC:20773): (tubulin beta 8 class VIII) The protein encoded by this gene represents the primary beta-tubulin subunit of oocytes and the early embryo. Defects in this gene, which is primate-specific, are a cause of oocyte maturation defect 2 and infertility. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TUBB8
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.752
PP5
?
Variant 10-47492-C-T is Pathogenic according to our data. Variant chr10-47492-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 223146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-47492-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB8 | NM_177987.3 | c.900G>A | p.Met300Ile | missense_variant | 4/4 | ENST00000568584.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB8 | ENST00000568584.6 | c.900G>A | p.Met300Ile | missense_variant | 4/4 | 1 | NM_177987.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oocyte maturation defect 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | literature only | SNPedia | Jan 21, 2016 | Infertility, female - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
0.037
.;.;B
Vest4
MutPred
0.81
.;.;Loss of catalytic residue at M300 (P = 0.0593);
MVP
ClinPred
D
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