Variant 5-14664892-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_138348.6(OTULIN):c.67C>A(p.Arg23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,169,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

OTULIN
NM_138348.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.173

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 5-14664892-C-A is Benign according to our data. Variant chr5-14664892-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1638016.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.173 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTULIN	NM_138348.6 linkuse as main transcript	c.67C>A	p.Arg23=	synonymous_variant	1/7	ENST00000284274.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OTULIN	ENST00000284274.5 linkuse as main transcript	c.67C>A	p.Arg23=	synonymous_variant	1/7	1	NM_138348.6	P1
OTULIN	ENST00000507335.1 linkuse as main transcript	n.161C>A		non_coding_transcript_exon_variant	1/2	2
OTULIN	ENST00000697367.1 linkuse as main transcript	c.67C>A	p.Arg23=	synonymous_variant, NMD_transcript_variant	1/5
OTULIN	ENST00000503023.2 linkuse as main transcript	c.67C>A	p.Arg23=	synonymous_variant, NMD_transcript_variant	1/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000983

AC:

AN:

142468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000584

AC:

AN:

1026558

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

484576

show subpopulations

Gnomad4 AFR exome

AF:

0.000297

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:

0.00

Gnomad4 OTH exome

AF:

0.0000254

GnomAD4 genome

AF:

0.0000982

AC:

AN:

142556

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

69844

show subpopulations

Gnomad4 AFR

AF:

0.000353

Gnomad4 AMR

AF:

0.000135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

Cadd

Benign

Dann

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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