rs17213861

Positions:

chr6-32858490-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_002800.5(PSMB9):c.517C>T(p.Arg173Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,612,920 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 21 hom. )

Consequence

PSMB9
NM_002800.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.657

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 6-32858490-C-T is Benign according to our data. Variant chr6-32858490-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1711625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB9	NM_002800.5 linkuse as main transcript	c.517C>T	p.Arg173Cys	missense_variant	5/6	ENST00000374859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB9	ENST00000374859.3 linkuse as main transcript	c.517C>T	p.Arg173Cys	missense_variant	5/6	1	NM_002800.5	P1	P28065-1
PSMB9	ENST00000395330.5 linkuse as main transcript	c.448C>T	p.Arg150Cys	missense_variant	5/6	3
PSMB9	ENST00000464863.1 linkuse as main transcript	n.2266C>T		non_coding_transcript_exon_variant	3/3	2
PSMB9	ENST00000467593.1 linkuse as main transcript	n.498C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00296

AC:

450

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00435

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00302

AC:

745

AN:

246542

Hom.:

AF XY:

0.00290

AC XY:

390

AN XY:

134398

show subpopulations

Gnomad AFR exome

AF:

0.000795

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.00569

Gnomad NFE exome

AF:

0.00518

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00478

AC:

6987

AN:

1460724

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

3333

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00688

Gnomad4 NFE exome

AF:

0.00573

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00296

AC:

450

AN:

152196

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00435

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00450

Hom.:

Bravo

AF:

0.00259

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00265

AC:

ESP6500EA

AF:

0.00554

AC:

ExAC

AF:

0.00351

AC:

412

EpiCase

AF:

0.00403

EpiControl

AF:

0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PSMB9-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 25, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

PSMB9: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.012

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

.;L

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.99

.;D

Vest4

0.26

MVP

0.31

MPC

0.56

ClinPred

0.031

GERP RS

4.0

Varity_R

0.18

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: -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