chr10-47356-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_177987.3(TUBB8):c.1036C>A(p.Pro346Thr) 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
Genomes: not found (cov: 27)
Consequence
TUBB8
NM_177987.3 missense
NM_177987.3 missense
Scores
6
5
5
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 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, 0.971
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB8 | NM_177987.3 | c.1036C>A | p.Pro346Thr | missense_variant | 4/4 | ENST00000568584.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB8 | ENST00000568584.6 | c.1036C>A | p.Pro346Thr | missense_variant | 4/4 | 1 | NM_177987.3 | P1 | |
TUBB8 | ENST00000564130.2 | c.934C>A | p.Pro312Thr | missense_variant | 4/4 | 5 | |||
TUBB8 | ENST00000568866.5 | c.925C>A | p.Pro309Thr | missense_variant | 3/3 | 5 | |||
TUBB8 | ENST00000561967.1 | c.*699C>A | 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: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oocyte maturation defect 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Apr 04, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
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
Pathogenic
D;D;D
Polyphen
1.0
.;.;D
Vest4
MutPred
0.89
.;.;Gain of ubiquitination at K350 (P = 0.1181);
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
Publications
No publications associated with this variant yet.