Variant 5-14664886-CCGGCGCGGGAGGCGGCGGCCA-CCGGCGCGGGAGGCGGCGGCCACGGCGCGGGAGGCGGCGGCCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_138348.6(OTULIN):c.72_92dupGGCGGCGGCCACGGCGCGGGA(p.Glu24_Arg30dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,020 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

OTULIN
NM_138348.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.907

Variant links:

Genes affected

OTULIN (HGNC:25118): (OTU deubiquitinase with linear linkage specificity) This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]

OTULIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_138348.6.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTULIN	NM_138348.6 link	c.72_92dupGGCGGCGGCCACGGCGCGGGA	p.Glu24_Arg30dup	disruptive_inframe_insertion	Exon 1 of 7	ENST00000284274.5	NP_612357.4	Q96BN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTULIN	ENST00000284274.5 link	c.72_92dupGGCGGCGGCCACGGCGCGGGA	p.Glu24_Arg30dup	disruptive_inframe_insertion	Exon 1 of 7	1	NM_138348.6	ENSP00000284274.4	Q96BN8
OTULIN	ENST00000503023.2 link	n.72_92dupGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000427016.1	D6RD57
OTULIN	ENST00000507335.1 link	n.166_186dupGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 2	2
OTULIN	ENST00000697367.1 link	n.72_92dupGGCGGCGGCCACGGCGCGGGA		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000513279.1	A0A8V8TKZ0

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151020

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73736

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over