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

Variant summary

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

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

Variant links:

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.00746

AC:

1874

AN:

251208

Hom.:

AF XY:

0.00746

AC XY:

1013

AN XY:

135794

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 SAS exome

AF:

0.00314

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

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00314

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.00883

Gnomad4 OTH exome

AF:

0.00561

GnomAD4 genome

AF:

0.00690

AC:

1051

AN:

152272

Hom.:

Cov.:

AF XY:

0.00762

AC XY:

567

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0263

Gnomad4 NFE

AF:

0.00863

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00750

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

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;.;.;.;.

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

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

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