chr10-47549-G-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PVS1BS1_Supporting
The NM_177987.3(TUBB8):āc.843C>Gā(p.Tyr281Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 139,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: š 0.0021 ( 0 hom., cov: 29)
Exomes š: 0.00039 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TUBB8
NM_177987.3 stop_gained
NM_177987.3 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 3.25
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.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 37 pathogenic variants in the truncated region.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00214 (299/139686) while in subpopulation SAS AF= 0.00288 (13/4510). AF 95% confidence interval is 0.00231. There are 0 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB8 | NM_177987.3 | c.843C>G | p.Tyr281Ter | stop_gained | 4/4 | ENST00000568584.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB8 | ENST00000568584.6 | c.843C>G | p.Tyr281Ter | stop_gained | 4/4 | 1 | NM_177987.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 298AN: 139572Hom.: 0 Cov.: 29
GnomAD3 genomes
AF:
AC:
298
AN:
139572
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000193 AC: 46AN: 238432Hom.: 0 AF XY: 0.000184 AC XY: 24AN XY: 130774
GnomAD3 exomes
AF:
AC:
46
AN:
238432
Hom.:
AF XY:
AC XY:
24
AN XY:
130774
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000389 AC: 537AN: 1382196Hom.: 0 Cov.: 33 AF XY: 0.000380 AC XY: 261AN XY: 687340
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
537
AN:
1382196
Hom.:
Cov.:
33
AF XY:
AC XY:
261
AN XY:
687340
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00214 AC: 299AN: 139686Hom.: 0 Cov.: 29 AF XY: 0.00223 AC XY: 153AN XY: 68496
GnomAD4 genome
AF:
AC:
299
AN:
139686
Hom.:
Cov.:
29
AF XY:
AC XY:
153
AN XY:
68496
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ExAC
AF:
AC:
3
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
CIC-rearranged sarcoma Other:1
not provided, no classification provided | literature only | Children's Cancer Therapy Development Institute | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;D;D
Vest4
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