chr3-184299384-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002808.5(PSMD2):c.118G>A(p.Asp40Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000778 in 1,400,170 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: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
PSMD2
NM_002808.5 missense
NM_002808.5 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 4.17
Genes affected
PSMD2 (HGNC:9559): (proteasome 26S subunit ubiquitin receptor, non-ATPase 2) 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 one of the non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.11241993).
BS2
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMD2 | NM_002808.5 | c.118G>A | p.Asp40Asn | missense_variant | 1/21 | ENST00000310118.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMD2 | ENST00000310118.9 | c.118G>A | p.Asp40Asn | missense_variant | 1/21 | 1 | NM_002808.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000820 AC: 3AN: 36602Hom.: 0 AF XY: 0.0000478 AC XY: 1AN XY: 20918
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GnomAD4 exome AF: 0.0000745 AC: 93AN: 1247982Hom.: 0 Cov.: 32 AF XY: 0.0000638 AC XY: 39AN XY: 611314
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74354
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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 submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.118G>A (p.D40N) alteration is located in exon 1 (coding exon 1) of the PSMD2 gene. This alteration results from a G to A substitution at nucleotide position 118, causing the aspartic acid (D) at amino acid position 40 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of glycosylation at K39 (P = 0.0301);Loss of glycosylation at K39 (P = 0.0301);
MVP
MPC
ClinPred
T
GERP RS
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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