Genetic Variant OTULIN:p.Pro7Pro (chr5-14664846-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_138348.6(OTULIN):c.21C>A(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,215,452 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 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

OTULIN
NM_138348.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Publications

0 publications found

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:

OTULIN-DT (HGNC:55368): (OTULIN divergent transcript)

OTULIN-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 5-14664846-C-A is Benign according to our data. Variant chr5-14664846-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1651398.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.18 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138348.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OTULIN	NM_138348.6	MANE Select	c.21C>A	p.Pro7Pro	synonymous	Exon 1 of 7	NP_612357.4
OTULIN-DT	NR_168439.1		n.-242G>T		upstream_gene	N/A
OTULIN-DT	NR_168440.1		n.-242G>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTULIN	ENST00000284274.5	TSL:1 MANE Select	c.21C>A	p.Pro7Pro	synonymous	Exon 1 of 7	ENSP00000284274.4	Q96BN8
OTULIN	ENST00000850613.1		c.21C>A	p.Pro7Pro	synonymous	Exon 1 of 8	ENSP00000520900.1	Q96BN8
OTULIN	ENST00000881544.1		c.21C>A	p.Pro7Pro	synonymous	Exon 1 of 6	ENSP00000551603.1

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

26020

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1063594

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

504602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22344

American (AMR)

AF:

0.00

AC:

AN:

10114

Ashkenazi Jewish (ASJ)

AF:

0.0000790

AC:

AN:

12660

East Asian (EAS)

AF:

0.00

AC:

AN:

24352

South Asian (SAS)

AF:

0.00

AC:

AN:

20870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2812

European-Non Finnish (NFE)

AF:

0.0000330

AC:

AN:

908494

Other (OTH)

AF:

0.0000241

AC:

AN:

41532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151858

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67908

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.1

(source)

DANN

Benign

0.84

PhyloP100

-1.2

PromoterAI

0.00040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over