dbSNP rs1177573: PSMD9:p.Arg134Trp (chr12-121899792-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002813.7(PSMD9):c.400C>T(p.Arg134Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,614,064 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 324 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 297 hom. )

Consequence

PSMD9
NM_002813.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

Publications

10 publications found

Variant links:

Genes affected

PSMD9 (HGNC:9567): (proteasome 26S subunit, non-ATPase 9) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 non-ATPase subunit of the 19S regulator. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2012]

PSMD9 links:

ENSG00000256950 (HGNC:):

ENSG00000256950 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016908348).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD9	NM_002813.7 link	c.400C>T	p.Arg134Trp	missense_variant	Exon 3 of 6	ENST00000541212.6	NP_002804.2	O00233-1
PSMD9	NM_001261400.3 link	c.139-3214C>T		intron_variant	Intron 1 of 3		NP_001248329.1	O00233-3
PSMD9	NR_048555.3 link	n.309-3214C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6 link	c.400C>T	p.Arg134Trp	missense_variant	Exon 3 of 6	1	NM_002813.7	ENSP00000440485.1		O00233-1
ENSG00000256950	ENST00000546333.1 link	n.242-3214C>T		intron_variant	Intron 2 of 3	5		ENSP00000477146.1		F5H7X1

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5563

AN:

152218

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0100

AC:

2517

AN:

250780

AF XY:

0.00757

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000716

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00405

AC:

5923

AN:

1461728

Hom.:

297

Cov.:

AF XY:

0.00352

AC XY:

2557

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.131

AC:

4388

AN:

33472

American (AMR)

AF:

0.00917

AC:

410

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000543

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000403

AC:

448

AN:

1111910

Other (OTH)

AF:

0.00949

AC:

573

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

351

702

1052

1403

1754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.0366

AC:

5576

AN:

152336

Hom.:

324

Cov.:

AF XY:

0.0360

AC XY:

2681

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.126

AC:

5247

AN:

41560

American (AMR)

AF:

0.0146

AC:

224

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68042

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

254

509

763

1018

1272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0263

Hom.:

222

Bravo

AF:

0.0418

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.123

AC:

544

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0122

AC:

1480

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;.

PhyloP100

2.4

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.16

MPC

0.53

ClinPred

0.044

GERP RS

1.7

Varity_R

0.064

gMVP

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

Other links and lift over