10-47499-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3 PP5

The NM_177987.3(TUBB8):c.893A>G(p.Asn298Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 29)
• Consequence: TUBB8 NM_177987.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.02

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 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, 0.758
• PP5: Variant 10-47499-T-C is Pathogenic according to our data. Variant chr10-47499-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 977680.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	c.893A>G	p.Asn298Ser	missense_variant	4/4	ENST00000568584.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB8	ENST00000568584.6	c.893A>G	p.Asn298Ser	missense_variant	4/4	1	NM_177987.3	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	16
Dann	Benign	0.84
Eigen	Benign	0.047
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	0.35	D
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.9	D;D;D
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.053	T;T;T
Polyphen		1.0	.;.;D
Vest4		0.48
MutPred		0.76		.;.;Loss of methylation at K297 (P = 0.0786);
MVP		0.88
ClinPred		0.94	D
Varity_R		0.83
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

Other links and lift over

dbSNP: rs1834359656; hg19: chr10-93439;