rs241419

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 82 Digenic 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

GnomAD3 exomes

AF:

0.0163

AC:

4020

AN:

246636

Hom.:

AF XY:

0.0156

AC XY:

2092

AN XY:

134396

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 SAS exome

AF:

0.00253

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

Gnomad4 AFR exome

AF:

0.0358

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.00723

Gnomad4 EAS exome

AF:

0.000730

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.00350

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0247

AC:

3765

AN:

152264

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1684

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0373

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0204

Hom.:

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

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

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

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