chr6-170543693-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002793.4(PSMB1):ā€‹c.341G>Cā€‹(p.Gly114Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000565 in 1,611,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000060 ( 0 hom. )

Consequence

PSMB1
NM_002793.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10
Variant links:
Genes affected
PSMB1 (HGNC:9537): (proteasome 20S subunit beta 1) 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. This gene is tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMB1NM_002793.4 linkuse as main transcriptc.341G>C p.Gly114Ala missense_variant 4/6 ENST00000262193.7 NP_002784.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMB1ENST00000262193.7 linkuse as main transcriptc.341G>C p.Gly114Ala missense_variant 4/61 NM_002793.4 ENSP00000262193 P1
PSMB1ENST00000462957.1 linkuse as main transcriptn.1556G>C non_coding_transcript_exon_variant 3/52

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152072
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250392
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135352
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000603
AC:
88
AN:
1459798
Hom.:
0
Cov.:
30
AF XY:
0.0000647
AC XY:
47
AN XY:
726272
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000756
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJul 05, 2023The c.341G>C (p.G114A) alteration is located in exon 4 (coding exon 4) of the PSMB1 gene. This alteration results from a G to C substitution at nucleotide position 341, causing the glycine (G) at amino acid position 114 to be replaced by an alanine (A). 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
0.12
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.035
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.0062
T
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.18
Sift
Benign
0.30
T
Sift4G
Benign
0.74
T
Polyphen
1.0
D
Vest4
0.83
MutPred
0.35
Gain of glycosylation at T113 (P = 0.089);
MVP
0.41
MPC
0.35
ClinPred
0.51
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748070247; hg19: chr6-170852781; API