10-47064-ACCTCCTCCTCGGCATACTCCTCATCCT-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_177987.3(TUBB8):c.1301_1327del(p.Glu434_Glu442del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000939 in 1,117,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: TUBB8 NM_177987.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.65

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB8	NM_177987.3	c.1301_1327del	p.Glu434_Glu442del	inframe_deletion	4/4	ENST00000568584.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB8	ENST00000568584.6	c.1301_1327del	p.Glu434_Glu442del	inframe_deletion	4/4	1	NM_177987.3	P1
TUBB8	ENST00000564130.2	c.1199_1225del	p.Glu400_Glu408del	inframe_deletion	4/4	5
TUBB8	ENST00000568866.5	c.1190_1216del	p.Glu397_Glu405del	inframe_deletion	3/3	5
TUBB8	ENST00000561967.1	c.*964_*990del		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.000111 AC: 16 AN: 143790 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000704

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: 0.000167

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000687 AC: 12 AN: 174636 Hom.: 0 AF XY: 0.0000642 AC XY: 6 AN XY: 93488

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000137

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000712

Gnomad NFE exome AF: 0.0000920

Gnomad OTH exome AF: 0.000436

GnomAD4 exome AF: 0.0000914 AC: 89 AN: 974158 Hom.: 0 AF XY: 0.0000821 AC XY: 41 AN XY: 499504

Gnomad4 AFR exome AF: 0.0000823

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000467

Gnomad4 EAS exome AF: 0.0000814

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000645

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.0000906

GnomAD4 genome AF: 0.000111 AC: 16 AN: 143790 Hom.: 0 Cov.: 21 AF XY: 0.000115 AC XY: 8 AN XY: 69510

Gnomad4 AFR AF: 0.000105

Gnomad4 AMR AF: 0.0000704

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000167

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000480 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

Apr 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs778521360; hg19: chr10-93004;