rs968719
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002805.6(PSMC5):c.655C>G(p.Leu219Val) variant causes a missense change involving the alteration of a non-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. Synonymous variant affecting the same amino acid position (i.e. L219L) has been classified as Benign.
Frequency
Genomes: not found (cov: 29)
Consequence
PSMC5
NM_002805.6 missense
NM_002805.6 missense
Scores
6
8
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.00700
Genes affected
PSMC5 (HGNC:9552): (proteasome 26S subunit, ATPase 5) 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 ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
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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, 0.929
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PSMC5 | NM_002805.6 | c.655C>G | p.Leu219Val | missense_variant | Exon 7 of 12 | ENST00000310144.11 | NP_002796.4 | |
| PSMC5 | NM_001199163.2 | c.631C>G | p.Leu211Val | missense_variant | Exon 7 of 12 | NP_001186092.1 | ||
| PSMC5 | XM_047436423.1 | c.655C>G | p.Leu219Val | missense_variant | Exon 7 of 8 | XP_047292379.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
29
GnomAD4 exome Cov.: 65
GnomAD4 exome
Cov.:
65
GnomAD4 genome
GnomAD4 genome
Cov.:
29
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;D;D;D;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D;D;D;D;D;D;.;D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L;.;.;.;.;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;D;.;.;.;.;.;D;.
REVEL
Uncertain
Sift
Uncertain
.;D;.;.;.;.;.;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
0.98
.;D;.;.;.;.;.;.;.
Vest4
0.83, 0.76
MutPred
0.76
.;Gain of MoRF binding (P = 0.1031);.;.;.;.;.;.;.;
MVP
MPC
2.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at