dbSNP rs2235587: PSMF1:p.His174Arg (chr20-1135276-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006814.5(PSMF1):c.521A>G(p.His174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,294 control chromosomes in the GnomAD database, including 24,298 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.14 ( 2051 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22247 hom. )

Consequence

PSMF1
NM_006814.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

PSMF1 (HGNC:9571): (proteasome inhibitor subunit 1) 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 protein that inhibits the activation of the proteasome by the 11S and 19S regulators. Alternative transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

PSMF1 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=1.3047457E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMF1	NM_006814.5 link	c.521A>G	p.His174Arg	missense_variant	Exon 4 of 7	ENST00000335877.11	NP_006805.2	Q92530A0A140VJT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMF1	ENST00000335877.11 link	c.521A>G	p.His174Arg	missense_variant	Exon 4 of 7	1	NM_006814.5	ENSP00000338039.6		Q92530

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20669

AN:

151978

Hom.:

2055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.183

AC:

45815

AN:

250550

Hom.:

5465

AF XY:

0.182

AC XY:

24685

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.475

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.162

AC:

236416

AN:

1461198

Hom.:

22247

Cov.:

AF XY:

0.163

AC XY:

118633

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.0269

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.136

AC:

20661

AN:

152096

Hom.:

2051

Cov.:

AF XY:

0.141

AC XY:

10496

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0320

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.157

Hom.:

4549

Bravo

AF:

0.136

TwinsUK

AF:

0.155

AC:

574

ALSPAC

AF:

0.149

AC:

574

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.150

AC:

1292

ExAC

AF:

0.177

AC:

21492

Asia WGS

AF:

0.281

AC:

979

AN:

3478

EpiCase

AF:

0.152

EpiControl

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.0034

T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

T;T;T;.

MetaRNN

Benign

0.00013

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.97

N;.;.;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.75

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.038

MPC

0.089

ClinPred

0.000016

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.37

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

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