rs2235587

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_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. 15/21 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 0.14 ( 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

Publications

31 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006814.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMF1	NM_006814.5	MANE Select	c.521A>G	p.His174Arg	missense	Exon 4 of 7	NP_006805.2	Q92530
PSMF1	NM_178578.4		c.521A>G	p.His174Arg	missense	Exon 5 of 8	NP_848693.2	Q92530
PSMF1	NM_001323408.2		c.521A>G	p.His174Arg	missense	Exon 4 of 7	NP_001310337.1	Q5QPM7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.521A>G	p.His174Arg	missense	Exon 4 of 7	ENSP00000338039.6	Q92530
PSMF1	ENST00000333082.7	TSL:1	c.521A>G	p.His174Arg	missense	Exon 5 of 8	ENSP00000327704.3	Q92530
PSMF1	ENST00000879397.1		c.521A>G	p.His174Arg	missense	Exon 4 of 8	ENSP00000549456.1

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

GnomAD2 exomes

AF:

0.183

AC:

45815

AN:

250550

AF XY:

0.182

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 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

African (AFR)

AF:

0.0269

AC:

901

AN:

33472

American (AMR)

AF:

0.206

AC:

9191

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5092

AN:

26084

East Asian (EAS)

AF:

0.492

AC:

19513

AN:

39684

South Asian (SAS)

AF:

0.207

AC:

17800

AN:

86198

European-Finnish (FIN)

AF:

0.165

AC:

8812

AN:

53412

Middle Eastern (MID)

AF:

0.144

AC:

818

AN:

5698

European-Non Finnish (NFE)

AF:

0.148

AC:

164428

AN:

1111610

Other (OTH)

AF:

0.163

AC:

9861

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

10852

21705

32557

43410

54262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6108

12216

18324

24432

30540

<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:

0.136

AC:

20661

AN:

152096

Hom.:

2051

Cov.:

AF XY:

0.141

AC XY:

10496

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0320

AC:

1328

AN:

41508

American (AMR)

AF:

0.200

AC:

3065

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

642

AN:

3470

East Asian (EAS)

AF:

0.474

AC:

2439

AN:

5148

South Asian (SAS)

AF:

0.222

AC:

1065

AN:

4806

European-Finnish (FIN)

AF:

0.160

AC:

1696

AN:

10600

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9977

AN:

67958

Other (OTH)

AF:

0.158

AC:

333

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

848

1696

2543

3391

4239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.151

Hom.:

6231

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

MetaRNN

Benign

0.00013

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.97

PhyloP100

1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

0.75

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.038

MPC

0.089

ClinPred

0.000016

GERP RS

2.9

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.37

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over