10-47525-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_177987.3(TUBB8):c.867T>C(p.Leu289=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00013 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBB8 NM_177987.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.278

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-47525-A-G is Benign according to our data. Variant chr10-47525-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2578610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.278 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB8	NM_177987.3	c.867T>C	p.Leu289=	synonymous_variant	4/4	ENST00000568584.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB8	ENST00000568584.6	c.867T>C	p.Leu289=	synonymous_variant	4/4	1	NM_177987.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 443 AN: 142698 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000901

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000617

Gnomad SAS AF: 0.000445

Gnomad FIN AF: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000168

Gnomad OTH AF: 0.00259

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000134 AC: 194 AN: 1447580 Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 78 AN XY: 720002

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 0.0000163

Gnomad4 OTH exome AF: 0.000320

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00309 AC: 442 AN: 142816 Hom.: 0 Cov.: 29 AF XY: 0.00302 AC XY: 211 AN XY: 69922

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.000900

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000618

Gnomad4 SAS AF: 0.000445

Gnomad4 FIN AF: 0.000197

Gnomad4 NFE AF: 0.000168

Gnomad4 OTH AF: 0.00256

Alfa AF: 0.00176 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

TUBB8: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.2
Dann	Benign	0.26

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: rs781796307; hg19: chr10-93465; COSMIC: COSV59115993; COSMIC: COSV59115993;