Genetic Variant NM_002798.3:c.319C>G (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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB6	NM_002798.3 link	c.319C>G	p.Pro107Ala	missense_variant	Exon 4 of 6	ENST00000270586.8	NP_002789.1	P28072Q6IAT9
PSMB6	NM_001270481.2 link	c.319C>G	p.Pro107Ala	missense_variant	Exon 4 of 6		NP_001257410.1	A0A087X2I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSMB6	ENST00000270586.8 link	c.319C>G	p.Pro107Ala	missense_variant	Exon 4 of 6	1	NM_002798.3	ENSP00000270586.3	P28072
PSMB6	ENST00000614486.4 link	c.319C>G	p.Pro107Ala	missense_variant	Exon 4 of 6	2		ENSP00000485006.1	A0A087X2I4
PSMB6	ENST00000575643.1 link	n.15C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
PSMB6	ENST00000571309.1 link	n.294-19C>G		intron_variant	Intron 3 of 5	3		ENSP00000460811.1	I3L3X7

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 v4.3

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

T;T

Eigen

Benign

0.010

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PhyloP100

2.9

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.071

Sift

Benign

0.13

.;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0

.;B

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over