rs1794109

Positions:

Variant summary

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

The NM_002817.4(PSMD13):​c.613C>T​(p.Leu205Phe) 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

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.81
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, 0.863

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMD13NM_002817.4 linkuse as main transcriptc.613C>T p.Leu205Phe missense_variant 8/13 ENST00000532097.6 NP_002808.3 Q9UNM6-1
PSMD13NM_175932.3 linkuse as main transcriptc.619C>T p.Leu207Phe missense_variant 6/11 NP_787128.2 Q9UNM6-2
PSMD13XM_011520235.4 linkuse as main transcriptc.613C>T p.Leu205Phe 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.613C>T p.Leu205Phe 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
0.89
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T;.;T;.;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.86
D;D;D;D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.7
M;.;.;.;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-3.3
D;D;D;.;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0040
D;D;D;.;D
Sift4G
Uncertain
0.048
D;T;T;T;D
Polyphen
0.82
P;P;.;.;.
Vest4
0.80
MutPred
0.73
Loss of stability (P = 0.125);.;.;Loss of stability (P = 0.125);Loss of stability (P = 0.125);
MVP
0.76
MPC
1.1
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.67
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs1794109; hg19: chr11-248820; API