Variant 10-47229-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP2PP3_ModeratePP5

The NM_177987.3(TUBB8):c.1163T>C(p.Met388Thr) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBB8
NM_177987.3 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.49

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 4 ACMG points.

PP2

Missense variant where missense usually causes diseases, TUBB8

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

PP5

Variant 10-47229-A-G is Pathogenic according to our data. Variant chr10-47229-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 977656.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.1163T>C	p.Met388Thr	missense_variant	4/4	ENST00000568584.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TUBB8	ENST00000568584.6 linkuse as main transcript	c.1163T>C	p.Met388Thr	missense_variant	4/4	1	NM_177987.3	P1
TUBB8	ENST00000564130.2 linkuse as main transcript	c.1061T>C	p.Met354Thr	missense_variant	4/4	5
TUBB8	ENST00000568866.5 linkuse as main transcript	c.1052T>C	p.Met351Thr	missense_variant	3/3	5
TUBB8	ENST00000561967.1 linkuse as main transcript	c.*826T>C		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.00000682

AC:

AN:

146620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725784

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000682

AC:

AN:

146620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71666

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000468

Hom.:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

Cadd

Benign

Dann

Benign

0.89

Eigen

Benign

0.099

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Uncertain

0.43

MutationTaster

Benign

0.71

D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.4

D;D;D

Sift

Uncertain

0.021

D;.;.

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.93

.;.;P

Vest4

0.67

MutPred

0.69

.;.;Loss of MoRF binding (P = 0.0937);

MVP

0.87

ClinPred

0.90

Varity_R

0.90

gMVP

0.95

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