rs11545172

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002808.5(PSMD2):c.526G>A(p.Ala176Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0425 in 1,614,156 control chromosomes in the GnomAD database, including 1,707 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.032 ( 131 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1576 hom. )

Consequence

PSMD2
NM_002808.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.17

Publications

15 publications found

Variant links:

Genes affected

PSMD2 (HGNC:9559): (proteasome 26S subunit ubiquitin receptor, non-ATPase 2) 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 one of the non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

PSMD2 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=0.0018980205).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD2	NM_002808.5 link	c.526G>A	p.Ala176Thr	missense_variant	Exon 5 of 21	ENST00000310118.9	NP_002799.3	Q13200-1
PSMD2	NM_001278708.2 link	c.136G>A	p.Ala46Thr	missense_variant	Exon 3 of 19		NP_001265637.1	Q13200-3
PSMD2	NM_001278709.2 link	c.49G>A	p.Ala17Thr	missense_variant	Exon 3 of 19		NP_001265638.1	Q13200-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD2	ENST00000310118.9 link	c.526G>A	p.Ala176Thr	missense_variant	Exon 5 of 21	1	NM_002808.5	ENSP00000310129.4		Q13200-1

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4866

AN:

152174

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00678

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0368

AC:

9261

AN:

251414

AF XY:

0.0387

show subpopulations

Gnomad AFR exome

AF:

0.00720

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0944

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0467

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0436

AC:

63761

AN:

1461864

Hom.:

1576

Cov.:

AF XY:

0.0440

AC XY:

31995

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00660

AC:

221

AN:

33480

American (AMR)

AF:

0.0178

AC:

798

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0970

AC:

2534

AN:

26134

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0375

AC:

3233

AN:

86258

European-Finnish (FIN)

AF:

0.0432

AC:

2307

AN:

53410

Middle Eastern (MID)

AF:

0.0603

AC:

348

AN:

5768

European-Non Finnish (NFE)

AF:

0.0465

AC:

51684

AN:

1111996

Other (OTH)

AF:

0.0435

AC:

2630

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4040

8081

12121

16162

20202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0319

AC:

4863

AN:

152292

Hom.:

131

Cov.:

AF XY:

0.0322

AC XY:

2395

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00676

AC:

281

AN:

41574

American (AMR)

AF:

0.0262

AC:

400

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

332

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.0332

AC:

160

AN:

4816

European-Finnish (FIN)

AF:

0.0385

AC:

409

AN:

10614

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3113

AN:

68012

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

240

481

721

962

1202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0397

Hom.:

322

Bravo

AF:

0.0300

TwinsUK

AF:

0.0440

AC:

163

ALSPAC

AF:

0.0457

AC:

176

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0490

AC:

421

ExAC

AF:

0.0365

AC:

4433

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0501

EpiControl

AF:

0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

PhyloP100

5.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.085

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.043

B;.;.

Vest4

0.10

MPC

0.67

ClinPred

0.0069

GERP RS

3.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.043

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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

rs11545172

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