10-47188-C-CAG

Variant names:

• chr10-47188-C-CAG
• rs1834348631
• NM_177987.3:c.1203_1204insCT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_177987.3(TUBB8):​c.1203_1204insCT​(p.Gly402LeufsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 26)
• Consequence: TUBB8 NM_177987.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.57

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_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-47188-C-CAG is Pathogenic according to our data. Variant chr10-47188-C-CAG is described in ClinVar as [Pathogenic]. Clinvar id is 977667.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB8	NM_177987.3	c.1203_1204insCT	p.Gly402LeufsTer15	frameshift_variant	Exon 4 of 4	ENST00000568584.6	NP_817124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB8	ENST00000568584.6	c.1203_1204insCT	p.Gly402LeufsTer15	frameshift_variant	Exon 4 of 4	1	NM_177987.3	ENSP00000456206.2
TUBB8	ENST00000564130.2	c.1101_1102insCT	p.Gly368LeufsTer15	frameshift_variant	Exon 4 of 4	5		ENSP00000457610.1
TUBB8	ENST00000568866.5	c.1092_1093insCT	p.Gly365LeufsTer15	frameshift_variant	Exon 3 of 3	5		ENSP00000457062.1
TUBB8	ENST00000561967	c.*866_*867insCT		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000454878.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 26

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Oocyte maturation defect 2 Pathogenic:1

Aug 31, 2020

Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

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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: rs1834348631; hg19: chr10-93128;