rs869025271
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_177987.3(TUBB8):c.686T>C(p.Val229Ala) 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: 35)
Consequence
TUBB8
NM_177987.3 missense
NM_177987.3 missense
Scores
2
5
9
Clinical Significance
Conservation
PhyloP100: 6.49
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 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, 0.92
PP5
?
Variant 10-47706-A-G is Pathogenic according to our data. Variant chr10-47706-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 221268.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-47706-A-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB8 | NM_177987.3 | c.686T>C | p.Val229Ala | missense_variant | 4/4 | ENST00000568584.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB8 | ENST00000568584.6 | c.686T>C | p.Val229Ala | missense_variant | 4/4 | 1 | NM_177987.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 35
GnomAD3 genomes
?
Cov.:
35
GnomAD4 exome Cov.: 70
GnomAD4 exome
Cov.:
70
GnomAD4 genome ? Cov.: 35
GnomAD4 genome
?
Cov.:
35
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oocyte maturation defect 2 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 10, 2023 | - - |
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;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
Sift
Uncertain
D;.;.
Sift4G
Benign
T;T;T
Polyphen
0.99
.;.;D
Vest4
MutPred
0.75
.;.;Gain of disorder (P = 0.0905);
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