dbSNP rs2297575: PSMD5:p.Glu21Gly (chr9-120842848-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005047.4(PSMD5):c.62A>G(p.Glu21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,607,506 control chromosomes in the GnomAD database, including 2,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 320 hom., cov: 33)

Exomes 𝑓: 0.017 ( 2096 hom. )

Consequence

PSMD5
NM_005047.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

10 publications found

Variant links:

Genes affected

PSMD5 (HGNC:9563): (proteasome 26S subunit, non-ATPase 5) 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. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]

PSMD5 links:

CUTALP (HGNC:):

CUTALP links:

CUTALP (HGNC:27367): (cutA divalent cation tolerance like, pseudogene)

CUTALP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0022414327).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD5	NM_005047.4 link	c.62A>G	p.Glu21Gly	missense_variant	Exon 1 of 10	ENST00000210313.8	NP_005038.1	Q16401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD5	ENST00000210313.8 link	c.62A>G	p.Glu21Gly	missense_variant	Exon 1 of 10	1	NM_005047.4	ENSP00000210313.2		Q16401-1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3820

AN:

152188

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00434

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00435

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0553

AC:

13057

AN:

236306

AF XY:

0.0443

show subpopulations

Gnomad AFR exome

AF:

0.00510

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.000980

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.0356

GnomAD4 exome

AF:

0.0172

AC:

25051

AN:

1455200

Hom.:

2096

Cov.:

AF XY:

0.0159

AC XY:

11503

AN XY:

723940

show subpopulations

African (AFR)

AF:

0.00293

AC:

AN:

33434

American (AMR)

AF:

0.235

AC:

10364

AN:

44146

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

414

AN:

26030

East Asian (EAS)

AF:

0.179

AC:

7104

AN:

39590

South Asian (SAS)

AF:

0.00947

AC:

813

AN:

85840

European-Finnish (FIN)

AF:

0.000984

AC:

AN:

49776

Middle Eastern (MID)

AF:

0.00354

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.00448

AC:

4973

AN:

1110906

Other (OTH)

AF:

0.0202

AC:

1217

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1234

2468

3701

4935

6169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.0252

AC:

3838

AN:

152306

Hom.:

320

Cov.:

AF XY:

0.0277

AC XY:

2066

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00433

AC:

180

AN:

41578

American (AMR)

AF:

0.138

AC:

2108

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3470

East Asian (EAS)

AF:

0.200

AC:

1032

AN:

5162

South Asian (SAS)

AF:

0.0176

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00437

AC:

297

AN:

68020

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

177

354

532

709

886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0159

Hom.:

187

Bravo

AF:

0.0382

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00373

AC:

ExAC

AF:

0.0431

AC:

5221

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

PhyloP100

2.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.4

N;N;.

REVEL

Benign

0.14

Sift

Benign

0.037

D;D;.

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.75

P;.;.

Vest4

0.45

MPC

0.10

ClinPred

0.078

GERP RS

5.2

PromoterAI

0.048

Neutral

(source)

Varity_R

0.32

gMVP

0.41

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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