chr10-47319-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3_ModeratePP5
The NM_177987.3(TUBB8):c.1073C>T(p.Pro358Leu) 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 Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P358A) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 27)
Consequence
TUBB8
NM_177987.3 missense
NM_177987.3 missense
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 6.94
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 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr10-47320-G-C is described in Lovd as [Pathogenic].
PP2
?
Missense variant where missense usually causes diseases, TUBB8
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.901
PP5
?
Variant 10-47319-G-A is Pathogenic according to our data. Variant chr10-47319-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 977671.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-47319-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB8 | NM_177987.3 | c.1073C>T | p.Pro358Leu | missense_variant | 4/4 | ENST00000568584.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB8 | ENST00000568584.6 | c.1073C>T | p.Pro358Leu | missense_variant | 4/4 | 1 | NM_177987.3 | P1 | |
TUBB8 | ENST00000564130.2 | c.971C>T | p.Pro324Leu | missense_variant | 4/4 | 5 | |||
TUBB8 | ENST00000568866.5 | c.962C>T | p.Pro321Leu | missense_variant | 3/3 | 5 | |||
TUBB8 | ENST00000561967.1 | c.*736C>T | 3_prime_UTR_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 27
GnomAD3 genomes
?
Cov.:
27
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 27
GnomAD4 genome
?
Cov.:
27
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Oocyte maturation defect 2 Pathogenic:1
Likely pathogenic, no assertion criteria provided | case-control | Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University | Aug 31, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
Sift
Pathogenic
D;.;.
Sift4G
Uncertain
T;T;T
Polyphen
1.0
.;.;D
Vest4
MutPred
0.76
.;.;Loss of catalytic residue at P357 (P = 0.0096);
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