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

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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

CUTALP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.0553

AC:

13057

AN:

236306

Hom.:

1457

AF XY:

0.0443

AC XY:

5750

AN XY:

129872

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 SAS exome

AF:

0.00924

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

Gnomad4 AFR exome

AF:

0.00293

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.00947

Gnomad4 FIN exome

AF:

0.000984

Gnomad4 NFE exome

AF:

0.00448

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0252

AC:

3838

AN:

152306

Hom.:

320

Cov.:

AF XY:

0.0277

AC XY:

2066

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00437

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0147

Hom.:

109

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

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;.

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

Varity_R

0.32

gMVP

0.41

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over