14-23042583-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099780.2(PSMB11):​c.358G>A​(p.Gly120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PSMB11
NM_001099780.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96
Variant links:
Genes affected
PSMB11 (HGNC:31963): (proteasome subunit beta 11) Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system. Proteolysis is conducted by 20S proteasomes, complexes of 28 subunits arranged as a cylinder in 4 heteroheptameric rings: alpha-1 to -7, beta-1 to -7, beta-1 to -7, and alpha-1 to -7. The catalytic subunits are beta-1 (PSMB6; MIM 600307), beta-2 (PSMB7; MIM 604030), and beta-5 (PSMB5; MIM 600306). Three additional subunits, beta-1i (PSMB9; MIM 177045), beta-2i (PSMB10; MIM 176847), and beta-5i (PSMB8; MIM 177046), are induced by gamma-interferon (IFNG; MIM 147570) and are preferentially incorporated into proteasomes to make immunoproteasomes. PSMB11, or beta-5t, is a catalytic subunit expressed exclusively in cortical thymic epithelial cells (Murata et al., 2007 [PubMed 17540904]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29978657).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMB11NM_001099780.2 linkuse as main transcriptc.358G>A p.Gly120Ser missense_variant 1/1 ENST00000408907.5 NP_001093250.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMB11ENST00000408907.5 linkuse as main transcriptc.358G>A p.Gly120Ser missense_variant 1/1 NM_001099780.2 ENSP00000386212 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461838
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 01, 2021The c.358G>A (p.G120S) alteration is located in exon 1 (coding exon 1) of the PSMB11 gene. This alteration results from a G to A substitution at nucleotide position 358, causing the glycine (G) at amino acid position 120 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.095
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
0.72
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.18
Sift
Benign
0.11
T
Sift4G
Benign
0.21
T
Polyphen
1.0
D
Vest4
0.35
MutPred
0.46
Gain of phosphorylation at G120 (P = 0.0195);
MVP
0.69
MPC
0.59
ClinPred
0.94
D
GERP RS
5.2
Varity_R
0.23
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23511792; API