Variant chr8-91078415-AAACTT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_016023.5(OTUD6B):c.379_383del(p.Leu127ArgfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OTUD6B
NM_016023.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 8.72

Variant links:

Genes affected

OTUD6B (HGNC:24281): (OTU deubiquitinase 6B) This gene encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Deubiquitinating enzymes are primarily involved in removing ubiquitin from proteins targeted for degradation. This protein may function as a negative regulator of the cell cycle in B cells. [provided by RefSeq, Nov 2013]

OTUD6B links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-91078415-AAACTT-A is Pathogenic according to our data. Variant chr8-91078415-AAACTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 375702.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OTUD6B	NM_016023.5 linkuse as main transcript	c.379_383del	p.Leu127ArgfsTer8	frameshift_variant	4/7	ENST00000404789.8	NP_057107.4
OTUD6B	NM_001286745.3 linkuse as main transcript	c.76_80del	p.Leu26ArgfsTer8	frameshift_variant	5/8		NP_001273674.1
OTUD6B	NM_001416022.1 linkuse as main transcript	c.298_302del	p.Leu100ArgfsTer8	frameshift_variant	3/6		NP_001402951.1
OTUD6B	XM_011517129.3 linkuse as main transcript	c.76_80del	p.Leu26ArgfsTer8	frameshift_variant	4/7		XP_011515431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8 linkuse as main transcript	c.379_383del	p.Leu127ArgfsTer8	frameshift_variant	4/7	1	NM_016023.5	ENSP00000384190		Q8N6M0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444836

Hom.:

AF XY:

0.00

AC XY:

AN XY:

716914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy;C0432072:Dysmorphic features;C3714756:Intellectual disability

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Baylor Genetics

Jan 09, 2017

This variant was observed in one family: 2 affected sibs were homozygous. 1 brother was 9yo, severe intellectual disability, epilepsy, IUGR, microcephalic, hypotonia, failure to thrive, cryptorchidism, dysmorphic features, broad thumbs. Second brother was 3yo, severe delays, epilepsy, IUGR, microcephaly, hypotonia, failure to thrive, cortical and white matter atrophy, sacral dimple, VSD, cryptorchidism, dysmorphic features. -

Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 03, 2017

- -

not provided

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes

Apr 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over