dbSNP rs1831036680: PSMB7:p.Met125Val (chr9-124412374-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002799.4(PSMB7):c.373A>G(p.Met125Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PSMB7
NM_002799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Publications

0 publications found

Variant links:

Genes affected

PSMB7 (HGNC:9544): (proteasome 20S subunit beta 7) 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. Expression of this catalytic subunit is downregulated by gamma interferon, and proteolytic processing is required to generate a mature subunit. A pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Jul 2012]

PSMB7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002799.4. 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
	PSMB7	NM_002799.4	MANE Select	c.373A>G	p.Met125Val	missense	Exon 4 of 8	NP_002790.1	Q99436-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMB7	ENST00000259457.8	TSL:1 MANE Select	c.373A>G	p.Met125Val	missense	Exon 4 of 8	ENSP00000259457.3	Q99436-1
PSMB7	ENST00000916860.1		c.373A>G	p.Met125Val	missense	Exon 4 of 9	ENSP00000586919.1
PSMB7	ENST00000894504.1		c.373A>G	p.Met125Val	missense	Exon 4 of 9	ENSP00000564563.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.059

Eigen

Benign

-0.11

Eigen_PC

Benign

0.00064

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

M_CAP

Benign

0.0075

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

6.2

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.1

REVEL

Benign

0.28

Sift

Uncertain

0.027

Sift4G

Benign

0.082

Polyphen

0.63

Vest4

0.85

MutPred

0.69

Gain of catalytic residue at M125 (P = 0.0145)

MVP

0.72

MPC

0.40

ClinPred

0.84

GERP RS

3.7

Varity_R

0.62

gMVP

0.95

Mutation Taster

=29/71

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over