rs241419

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002800.5(PSMB9):c.94G>A(p.Val32Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0244 in 1,612,750 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 82 hom., cov: 31)

Exomes 𝑓: 0.024 ( 539 hom. )

Consequence

PSMB9
NM_002800.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.07

Publications

27 publications found

Variant links:

Genes affected

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

PSMB9 Gene-Disease associations (from GenCC):

proteasome-associated autoinflammatory syndrome 3
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

PSMB9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006846845).

BP6

Variant 6-32856171-G-A is Benign according to our data. Variant chr6-32856171-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056957.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0247 (3765/152264) while in subpopulation AFR AF = 0.0373 (1550/41534). AF 95% confidence interval is 0.0358. There are 82 homozygotes in GnomAd4. There are 1684 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 82 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB9	NM_002800.5 link	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 6	ENST00000374859.3	NP_002791.1	P28065-1A0A1U9X8D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000374859.3 link	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 6	1	NM_002800.5	ENSP00000363993.2		P28065-1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3762

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0163

AC:

4020

AN:

246636

AF XY:

0.0156

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.00662

Gnomad EAS exome

AF:

0.00284

Gnomad FIN exome

AF:

0.00328

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0243

AC:

35510

AN:

1460486

Hom.:

539

Cov.:

AF XY:

0.0232

AC XY:

16867

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.0358

AC:

1197

AN:

33470

American (AMR)

AF:

0.0210

AC:

938

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00723

AC:

189

AN:

26134

East Asian (EAS)

AF:

0.000730

AC:

AN:

39700

South Asian (SAS)

AF:

0.00276

AC:

238

AN:

86252

European-Finnish (FIN)

AF:

0.00350

AC:

183

AN:

52328

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0282

AC:

31300

AN:

1111758

Other (OTH)

AF:

0.0229

AC:

1381

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1746

3492

5239

6985

8731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1264

2528

3792

5056

6320

<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:

0.0247

AC:

3765

AN:

152264

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1684

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0373

AC:

1550

AN:

41534

American (AMR)

AF:

0.0310

AC:

474

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.00311

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0233

AC:

1586

AN:

68014

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

193

387

580

774

967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0219

Hom.:

159

Bravo

AF:

0.0280

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.0367

AC:

111

ESP6500EA

AF:

0.0238

AC:

129

ExAC

AF:

0.0155

AC:

1831

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0235

EpiControl

AF:

0.0248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSMB9-related disorder

Benign:1

Jul 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

2.0

.;.;M

PhyloP100

5.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.90

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.15

MPC

0.39

ClinPred

0.047

GERP RS

5.4

Varity_R

0.28

gMVP

0.53

Mutation Taster

=93/7

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over