Genetic Variant PSMB6:p.Pro107Ala (chr17-4797698-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002798.3(PSMB6):c.319C>G(p.Pro107Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,614,050 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.014 ( 56 hom., cov: 32)

Exomes 𝑓: 0.016 ( 475 hom. )

Consequence

PSMB6
NM_002798.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.89

Publications

16 publications found

Variant links:

Genes affected

PSMB6 (HGNC:9543): (proteasome 20S subunit beta 6) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. The encoded protein is a member of the proteasome B-type family, also known as the T1B family, and is a 20S core beta subunit in the proteasome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

PSMB6 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=0.0017100871).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002798.3. 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
	PSMB6	NM_002798.3	MANE Select	c.319C>G	p.Pro107Ala	missense	Exon 4 of 6	NP_002789.1	Q6IAT9
	PSMB6	NM_001270481.2		c.319C>G	p.Pro107Ala	missense	Exon 4 of 6	NP_001257410.1	A0A087X2I4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMB6	ENST00000270586.8	TSL:1 MANE Select	c.319C>G	p.Pro107Ala	missense	Exon 4 of 6	ENSP00000270586.3	P28072
PSMB6	ENST00000939639.1		c.325C>G	p.Pro109Ala	missense	Exon 4 of 6	ENSP00000609698.1
PSMB6	ENST00000939638.1		c.298C>G	p.Pro100Ala	missense	Exon 4 of 6	ENSP00000609697.1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2170

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0469

Gnomad FIN

AF:

0.00906

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00923

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0257

AC:

6468

AN:

251338

AF XY:

0.0250

show subpopulations

Gnomad AFR exome

AF:

0.00338

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.00636

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.00795

Gnomad NFE exome

AF:

0.00976

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0162

AC:

23626

AN:

1461860

Hom.:

475

Cov.:

AF XY:

0.0167

AC XY:

12161

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

33478

American (AMR)

AF:

0.0433

AC:

1938

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00612

AC:

160

AN:

26134

East Asian (EAS)

AF:

0.106

AC:

4191

AN:

39698

South Asian (SAS)

AF:

0.0450

AC:

3880

AN:

86258

European-Finnish (FIN)

AF:

0.00841

AC:

449

AN:

53418

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0106

AC:

11801

AN:

1111994

Other (OTH)

AF:

0.0182

AC:

1100

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

1349

2698

4048

5397

6746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.0142

AC:

2168

AN:

152190

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1129

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00347

AC:

144

AN:

41526

American (AMR)

AF:

0.0270

AC:

412

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

604

AN:

5172

South Asian (SAS)

AF:

0.0467

AC:

225

AN:

4818

European-Finnish (FIN)

AF:

0.00906

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00923

AC:

628

AN:

68018

Other (OTH)

AF:

0.0152

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0116

Hom.:

Bravo

AF:

0.0147

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.0238

AC:

2889

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

EpiCase

AF:

0.00965

EpiControl

AF:

0.00806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.028

Eigen

Benign

0.010

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

2.9

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

REVEL

Benign

0.071

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.13

MPC

0.49

ClinPred

0.017

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.80

Mutation Taster

=97/3

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

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