rs1794108

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002817.4(PSMD13):​c.611G>A​(p.Gly204Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

PSMD13
NM_002817.4 missense

Scores

7
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.87
Variant links:
Genes affected
PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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 non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMD13NM_002817.4 linkuse as main transcriptc.611G>A p.Gly204Glu missense_variant 8/13 ENST00000532097.6 NP_002808.3 Q9UNM6-1
PSMD13NM_175932.3 linkuse as main transcriptc.617G>A p.Gly206Glu missense_variant 6/11 NP_787128.2 Q9UNM6-2
PSMD13XM_011520235.4 linkuse as main transcriptc.611G>A p.Gly204Glu missense_variant 8/11 XP_011518537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMD13ENST00000532097.6 linkuse as main transcriptc.611G>A p.Gly204Glu missense_variant 8/131 NM_002817.4 ENSP00000436186.1 Q9UNM6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.087
T;.;T;.;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Pathogenic
0.93
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.;.;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-2.0
N;N;N;.;N
REVEL
Uncertain
0.50
Sift
Uncertain
0.0020
D;D;D;.;D
Sift4G
Uncertain
0.0030
D;D;D;D;D
Polyphen
0.99
D;D;.;.;.
Vest4
0.86
MutPred
0.86
Loss of catalytic residue at A203 (P = 0.0485);.;.;Loss of catalytic residue at A203 (P = 0.0485);Loss of catalytic residue at A203 (P = 0.0485);
MVP
0.76
MPC
1.1
ClinPred
0.92
D
GERP RS
5.5
Varity_R
0.79
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1794108; hg19: chr11-248818; API