20-1118880-T-G

Variant names:

Variant summary

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

The NM_006814.5(PSMF1):c.107T>G(p.Phe36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,732 control chromosomes in the GnomAD database, including 532,946 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 0.80 ( 49459 hom., cov: 33)

Exomes 𝑓: 0.81 ( 483487 hom. )

Consequence

PSMF1
NM_006814.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0830

Publications

44 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=9.395921E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 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.107T>G	p.Phe36Cys	missense	Exon 1 of 7	NP_006805.2	Q92530
PSMF1	NM_178578.4		c.107T>G	p.Phe36Cys	missense	Exon 2 of 8	NP_848693.2	Q92530
PSMF1	NM_001323408.2		c.107T>G	p.Phe36Cys	missense	Exon 1 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.107T>G	p.Phe36Cys	missense	Exon 1 of 7	ENSP00000338039.6	Q92530
PSMF1	ENST00000333082.7	TSL:1	c.107T>G	p.Phe36Cys	missense	Exon 2 of 8	ENSP00000327704.3	Q92530
PSMF1	ENST00000879397.1		c.107T>G	p.Phe36Cys	missense	Exon 1 of 8	ENSP00000549456.1

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122070

AN:

152080

Hom.:

49416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.830

Gnomad OTH

AF:

0.789

GnomAD2 exomes

AF:

0.782

AC:

195182

AN:

249594

AF XY:

0.784

show subpopulations

Gnomad AFR exome

AF:

0.815

Gnomad AMR exome

AF:

0.779

Gnomad ASJ exome

AF:

0.789

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.784

GnomAD4 exome

AF:

0.811

AC:

1184745

AN:

1461534

Hom.:

483487

Cov.:

AF XY:

0.810

AC XY:

588668

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.816

AC:

27307

AN:

33470

American (AMR)

AF:

0.777

AC:

34756

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

20527

AN:

26130

East Asian (EAS)

AF:

0.454

AC:

18037

AN:

39696

South Asian (SAS)

AF:

0.768

AC:

66223

AN:

86254

European-Finnish (FIN)

AF:

0.798

AC:

42572

AN:

53366

Middle Eastern (MID)

AF:

0.820

AC:

4729

AN:

5766

European-Non Finnish (NFE)

AF:

0.830

AC:

922262

AN:

1111748

Other (OTH)

AF:

0.800

AC:

48332

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12226

24452

36679

48905

61131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20942

41884

62826

83768

104710

<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:

0.803

AC:

122176

AN:

152198

Hom.:

49459

Cov.:

AF XY:

0.797

AC XY:

59298

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.816

AC:

33890

AN:

41540

American (AMR)

AF:

0.773

AC:

11823

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.794

AC:

2758

AN:

3472

East Asian (EAS)

AF:

0.475

AC:

2450

AN:

5156

South Asian (SAS)

AF:

0.751

AC:

3622

AN:

4826

European-Finnish (FIN)

AF:

0.798

AC:

8436

AN:

10578

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.830

AC:

56451

AN:

68010

Other (OTH)

AF:

0.792

AC:

1673

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1262

2524

3787

5049

6311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.815

Hom.:

193277

Bravo

AF:

0.801

TwinsUK

AF:

0.823

AC:

3052

ALSPAC

AF:

0.828

AC:

3190

ESP6500AA

AF:

0.812

AC:

3576

ESP6500EA

AF:

0.829

AC:

7131

ExAC

AF:

0.785

AC:

95338

Asia WGS

AF:

0.648

AC:

2254

AN:

3478

EpiCase

AF:

0.827

EpiControl

AF:

0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0062

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.053

MetaRNN

Benign

9.4e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-0.083

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.030

REVEL

Benign

0.11

Sift

Benign

0.097

Sift4G

Uncertain

0.048

Polyphen

0.0

Vest4

0.091

MPC

0.11

ClinPred

0.0052

GERP RS

1.9

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.093

gMVP

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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