rs35100697

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002800.5(PSMB9):c.26G>A(p.Gly9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,534,740 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0082 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 63 hom. )

Consequence

PSMB9
NM_002800.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.36

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041626394).

BP6

Variant 6-32854255-G-A is Benign according to our data. Variant chr6-32854255-G-A is described in ClinVar as [Benign]. Clinvar id is 3044101.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0082 (1249/152318) while in subpopulation AFR AF= 0.026 (1081/41574). AF 95% confidence interval is 0.0247. There are 22 homozygotes in gnomad4. There are 636 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 22 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB9	NM_002800.5 linkuse as main transcript	c.26G>A	p.Gly9Glu	missense_variant	1/6	ENST00000374859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB9	ENST00000374859.3 linkuse as main transcript	c.26G>A	p.Gly9Glu	missense_variant	1/6	1	NM_002800.5	P1	P28065-1
PSMB9	ENST00000395330.5 linkuse as main transcript	c.-9-1883G>A		intron_variant		3
PSMB9	ENST00000414474.5 linkuse as main transcript	c.-9-1883G>A		intron_variant		5
PSMB9	ENST00000464863.1 linkuse as main transcript	n.108G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00821

AC:

1249

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00559

AC:

760

AN:

136046

Hom.:

AF XY:

0.00635

AC XY:

464

AN XY:

73092

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000298

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000338

Gnomad OTH exome

AF:

0.00503

GnomAD4 exome

AF:

0.00244

AC:

3368

AN:

1382422

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2023

AN XY:

682200

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000198

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00820

AC:

1249

AN:

152318

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

636

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00852

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0202

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00371

AC:

405

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PSMB9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2019

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

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.73

REVEL

Benign

0.028

Sift

Benign

0.032

Sift4G

Benign

0.26

Vest4

0.23

MVP

0.40

MPC

0.53

ClinPred

0.0055

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.092

gMVP

0.59

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