Variant 10-47454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_177987.3(TUBB8):c.938C>T(p.Ala313Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0045 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBB8
NM_177987.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 4.72

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 Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBB8. . Trascript score misZ: 3.4713 (greater than threshold 3.09). The gene has 36 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. GenCC has associacion of the gene with oocyte maturation defect 2.

BP4

Computational evidence support a benign effect (MetaRNN=0.065457165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8	NM_177987.3 link	c.938C>T	p.Ala313Val	missense_variant	4/4	ENST00000568584.6	NP_817124.1	Q3ZCM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB8	ENST00000568584.6 link	c.938C>T	p.Ala313Val	missense_variant	4/4	1	NM_177987.3	ENSP00000456206.2		Q3ZCM7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

619

AN:

137228

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00262

Gnomad AMR

AF:

0.00429

Gnomad ASJ

AF:

0.00186

Gnomad EAS

AF:

0.00138

Gnomad SAS

AF:

0.00247

Gnomad FIN

AF:

0.00182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.00633

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000188

AC:

264

AN:

1401064

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

149

AN XY:

696006

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.000383

Gnomad4 ASJ exome

AF:

0.000161

Gnomad4 EAS exome

AF:

0.000664

Gnomad4 SAS exome

AF:

0.000583

Gnomad4 FIN exome

AF:

0.000507

Gnomad4 NFE exome

AF:

0.0000826

Gnomad4 OTH exome

AF:

0.000227

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00451

AC:

620

AN:

137324

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

332

AN XY:

67026

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.00428

Gnomad4 ASJ

AF:

0.00186

Gnomad4 EAS

AF:

0.00138

Gnomad4 SAS

AF:

0.00224

Gnomad4 FIN

AF:

0.00182

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.00626

Alfa

AF:

0.00821

Hom.:

ExAC

AF:

0.0000838

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

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

- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

3.5

DANN

Benign

0.64

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.080

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.88

N;N;N

Sift

Benign

1.0

T;.;.

Sift4G

Benign

0.94

T;T;T

Polyphen

0.013

.;.;B

Vest4

0.22

MVP

0.37

ClinPred

0.013

Varity_R

0.069

gMVP

0.76

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