Variant 10-47347-C-T 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.1045G>A(p.Val349Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000549 in 1,457,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000055 ( 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: 3.98

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=0.016935527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8	NM_177987.3 link	c.1045G>A	p.Val349Ile	missense_variant	4/4	ENST00000568584.6	NP_817124.1	Q3ZCM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBB8	ENST00000568584.6 link	c.1045G>A	p.Val349Ile	missense_variant	4/4	1	NM_177987.3	ENSP00000456206.2	Q3ZCM7
TUBB8	ENST00000564130.2 link	c.943G>A	p.Val315Ile	missense_variant	4/4	5		ENSP00000457610.1	Q5SQY0
TUBB8	ENST00000568866.5 link	c.934G>A	p.Val312Ile	missense_variant	3/3	5		ENSP00000457062.1	A0A075B736
TUBB8	ENST00000561967 link	c.*708G>A		3_prime_UTR_variant	4/4	5		ENSP00000454878.1	A0A075B724

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

427

AN:

141612

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000451

Gnomad OTH

AF:

0.00153

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457114

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724720

show subpopulations

Gnomad4 AFR exome

AF:

0.000220

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00301

AC:

427

AN:

141714

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

208

AN XY:

69214

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.000221

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000452

Gnomad4 OTH

AF:

0.00152

ExAC

AF:

0.000231

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

0.086

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.17

.;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.39

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.44

N;N;N

Sift

Uncertain

0.025

D;.;.

Sift4G

Benign

0.42

T;T;T

Polyphen

0.11

.;.;B

Vest4

0.34

MVP

0.76

ClinPred

0.55

Varity_R

0.21

gMVP

0.75

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