10-47454-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 4.72

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP2: Missense variant where missense usually causes diseases, TUBB8
• BP4: Computational evidence support a benign effect (MetaRNN=0.065457165).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB8	ENST00000568584.6	c.938C>T	p.Ala313Val	missense_variant	4/4	1	NM_177987.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 619 AN: 137228 Hom.: 0 Cov.: 28 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.: 0 Cov.: 31 AF XY: 0.000214 AC XY: 149 AN XY: 696006

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.: 0 Cov.: 28 AF XY: 0.00495 AC XY: 332 AN XY: 67026

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.: 0

ExAC AF: 0.0000838 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	3.5
Dann	Benign	0.64
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.71	T
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	T
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

Other links and lift over

dbSNP: rs199826048; hg19: chr10-93394; COSMIC: COSV59115704; COSMIC: COSV59115704;