dbSNP rs28927679: PSMD13:p.Ser150Leu (chr11-247329-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002817.4(PSMD13):c.449C>T(p.Ser150Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00803 in 1,613,980 control chromosomes in the GnomAD database, including 75 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 0.0069 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 66 hom. )

Consequence

PSMD13
NM_002817.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.93

Publications

13 publications found

Variant links:

COSMIC-nc: COSV61500853

Genes affected

PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PSMD13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011199743).

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD13	NM_002817.4 link	c.449C>T	p.Ser150Leu	missense_variant	Exon 7 of 13	ENST00000532097.6	NP_002808.3	Q9UNM6-1
PSMD13	NM_175932.3 link	c.455C>T	p.Ser152Leu	missense_variant	Exon 5 of 11		NP_787128.2	Q9UNM6-2
PSMD13	XM_011520235.4 link	c.449C>T	p.Ser150Leu	missense_variant	Exon 7 of 11		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6 link	c.449C>T	p.Ser150Leu	missense_variant	Exon 7 of 13	1	NM_002817.4	ENSP00000436186.1		Q9UNM6-1

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1051

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00863

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00746

AC:

1874

AN:

251208

AF XY:

0.00746

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.00926

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00815

AC:

11911

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

5789

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

33470

American (AMR)

AF:

0.00175

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00295

AC:

AN:

26132

East Asian (EAS)

AF:

0.000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00314

AC:

271

AN:

86228

European-Finnish (FIN)

AF:

0.0232

AC:

1240

AN:

53418

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00883

AC:

9815

AN:

1111914

Other (OTH)

AF:

0.00561

AC:

339

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

587

1174

1761

2348

2935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.00690

AC:

1051

AN:

152272

Hom.:

Cov.:

AF XY:

0.00762

AC XY:

567

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41564

American (AMR)

AF:

0.00229

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3466

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0263

AC:

279

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00863

AC:

587

AN:

68024

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

108

162

216

270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00795

Hom.:

Bravo

AF:

0.00484

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00764

AC:

928

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;.;T;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

D;D;D;D;D

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PhyloP100

4.9

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.6

D;D;D;.;N

REVEL

Benign

0.21

Sift

Benign

0.066

T;D;D;.;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.95

P;D;.;.;.

Vest4

0.79

MVP

0.59

MPC

0.31

ClinPred

0.020

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.59

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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