14-24145152-T-G

Variant names:

Variant summary

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

The NM_002818.3(PSME2):c.266A>C(p.His89Pro) variant causes a missense change. The variant allele was found at a frequency of 0.993 in 152,252 control chromosomes in the GnomAD database, including 75,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H89L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.99 ( 75098 hom., cov: 30)

Exomes 𝑓: 0.99 ( 716676 hom. )

Failed GnomAD Quality Control

Consequence

PSME2
NM_002818.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Publications

33 publications found

Variant links:

Genes affected

PSME2 (HGNC:9569): (proteasome activator subunit 2) 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. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the beta subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three beta and three alpha subunits combine to form a heterohexameric ring. Six pseudogenes have been identified on chromosomes 4, 5, 8, 10 and 13. [provided by RefSeq, Jul 2008]

PSME2 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=5.717483E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSME2	NM_002818.3	MANE Select	c.266A>C	p.His89Pro	missense	Exon 6 of 11	NP_002809.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSME2	ENST00000216802.10	TSL:1 MANE Select	c.266A>C	p.His89Pro	missense	Exon 6 of 11	ENSP00000216802.5	Q9UL46
PSME2	ENST00000615264.4	TSL:5	c.311A>C	p.His104Pro	missense	Exon 6 of 11	ENSP00000484569.1	A0A087X1Z3
PSME2	ENST00000857133.1		c.263A>C	p.His88Pro	missense	Exon 6 of 11	ENSP00000527192.1

Frequencies

GnomAD3 genomes

AF:

0.993

AC:

151101

AN:

152134

Hom.:

75039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.990

Gnomad OTH

AF:

0.989

GnomAD2 exomes

AF:

0.993

AC:

249365

AN:

251182

AF XY:

0.992

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.990

AC:

1447145

AN:

1461128

Hom.:

716676

Cov.:

AF XY:

0.990

AC XY:

719981

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.998

AC:

33390

AN:

33458

American (AMR)

AF:

0.994

AC:

44454

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.989

AC:

25835

AN:

26128

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39698

South Asian (SAS)

AF:

0.997

AC:

85949

AN:

86240

European-Finnish (FIN)

AF:

0.998

AC:

53292

AN:

53420

Middle Eastern (MID)

AF:

0.991

AC:

5706

AN:

5758

European-Non Finnish (NFE)

AF:

0.989

AC:

1098937

AN:

1111354

Other (OTH)

AF:

0.992

AC:

59884

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

773

1546

2319

3092

3865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.993

AC:

151219

AN:

152252

Hom.:

75098

Cov.:

AF XY:

0.994

AC XY:

73962

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.998

AC:

41437

AN:

41532

American (AMR)

AF:

0.991

AC:

15149

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.989

AC:

3433

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5184

AN:

5184

South Asian (SAS)

AF:

0.998

AC:

4808

AN:

4820

European-Finnish (FIN)

AF:

0.998

AC:

10592

AN:

10610

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.990

AC:

67323

AN:

68024

Other (OTH)

AF:

0.989

AC:

2091

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.990

Hom.:

158096

Bravo

AF:

0.993

TwinsUK

AF:

0.990

AC:

3672

ALSPAC

AF:

0.988

AC:

3806

ESP6500AA

AF:

0.998

AC:

4398

ESP6500EA

AF:

0.989

AC:

8507

ExAC

AF:

0.993

AC:

120548

Asia WGS

AF:

0.999

AC:

3475

AN:

3478

EpiCase

AF:

0.990

EpiControl

AF:

0.989

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.025

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.031

MetaRNN

Benign

5.7e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-3.0

PhyloP100

4.3

PrimateAI

Uncertain

0.69

PROVEAN

Benign

3.2

REVEL

Benign

0.091

Sift

Benign

0.68

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MPC

0.85

ClinPred

0.0054

GERP RS

4.4

Varity_R

0.083

gMVP

0.48

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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