Genetic Variant NM_002794.5:c.485A>C (chr1-35605246-T-G) – 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_002794.5(PSMB2):c.485A>C(p.Lys162Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K162E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PSMB2
NM_002794.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.88

Publications

0 publications found

Variant links:

Genes affected

PSMB2 (HGNC:9539): (proteasome 20S subunit beta 2) 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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

PSMB2 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_002794.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMB2	NM_002794.5	MANE Select	c.485A>C	p.Lys162Thr	missense	Exon 5 of 6	NP_002785.1	P49721
PSMB2	NM_001199779.2		c.410A>C	p.Lys137Thr	missense	Exon 5 of 6	NP_001186708.1	B7Z478
PSMB2	NM_001199780.2		c.134A>C	p.Lys45Thr	missense	Exon 4 of 5	NP_001186709.1	A0A087WVV1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMB2	ENST00000373237.4	TSL:1 MANE Select	c.485A>C	p.Lys162Thr	missense	Exon 5 of 6	ENSP00000362334.3	P49721
PSMB2	ENST00000621781.4	TSL:1	c.134A>C	p.Lys45Thr	missense	Exon 4 of 5	ENSP00000479706.1	A0A087WVV1
PSMB2	ENST00000630477.1	TSL:1	n.373A>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.22

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

PhyloP100

6.9

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.22

Sift

Benign

0.065

Sift4G

Benign

0.064

Polyphen

0.096

Vest4

0.80

MutPred

0.59

Loss of stability (P = 0.1476)

MVP

0.52

MPC

1.2

ClinPred

0.96

GERP RS

6.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.71

gMVP

0.85

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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