Variant 10-47470-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5

The NM_177987.3(TUBB8):c.922G>A(p.Gly308Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,612,292 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 Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

TUBB8
NM_177987.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.57

Variant links:

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]

TUBB8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 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, 0.76

PP5

Variant 10-47470-C-T is Pathogenic according to our data. Variant chr10-47470-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 996214.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB8	NM_177987.3 linkuse as main transcript	c.922G>A	p.Gly308Ser	missense_variant	4/4	ENST00000568584.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB8	ENST00000568584.6 linkuse as main transcript	c.922G>A	p.Gly308Ser	missense_variant	4/4	1	NM_177987.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000970

AC:

AN:

247408

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000418

AC:

AN:

1459944

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

726310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000564

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

ExAC

AF:

0.000100

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oocyte maturation defect 2

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Strasbourg University Hospital

Feb 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

0.13

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.56

MutationTaster

Benign

0.94

D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.5

D;D;D

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.67

MVP

0.90

ClinPred

0.94

Varity_R

0.88

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over