chr20-1163153-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006814.5(PSMF1):c.575T>C(p.Val192Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00338 in 1,614,154 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 45 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 59 hom. )
Consequence
PSMF1
NM_006814.5 missense
NM_006814.5 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 4.83
Genes affected
PSMF1 (HGNC:9571): (proteasome inhibitor subunit 1) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 protein that inhibits the activation of the proteasome by the 11S and 19S regulators. Alternative transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0014114082).
BP6
?
Variant 20-1163153-T-C is Benign according to our data. Variant chr20-1163153-T-C is described in ClinVar as [Benign]. Clinvar id is 785834.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2196/152306) while in subpopulation AFR AF= 0.0467 (1940/41552). AF 95% confidence interval is 0.045. There are 45 homozygotes in gnomad4. There are 1016 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 45 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMF1 | NM_006814.5 | c.575T>C | p.Val192Ala | missense_variant | 5/7 | ENST00000335877.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMF1 | ENST00000335877.11 | c.575T>C | p.Val192Ala | missense_variant | 5/7 | 1 | NM_006814.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0144 AC: 2191AN: 152188Hom.: 45 Cov.: 32
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GnomAD3 exomes AF: 0.00469 AC: 1179AN: 251366Hom.: 27 AF XY: 0.00392 AC XY: 533AN XY: 135854
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GnomAD4 exome AF: 0.00223 AC: 3265AN: 1461848Hom.: 59 Cov.: 31 AF XY: 0.00201 AC XY: 1463AN XY: 727230
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GnomAD4 genome ? AF: 0.0144 AC: 2196AN: 152306Hom.: 45 Cov.: 32 AF XY: 0.0136 AC XY: 1016AN XY: 74488
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ESP6500AA
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MVP
MPC
0.088
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at