17-63829863-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002805.6(PSMC5):​c.178C>T​(p.Arg60Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PSMC5
NM_002805.6 missense

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62
Variant links:
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]
FTSJ3 (HGNC:17136): (FtsJ RNA 2'-O-methyltransferase 3) Although the function of this gene is not known, the existence of this gene is supported by mRNA and EST data. A possible function of the encoded protein can be inferred from amino acid sequence similarity to the E.coli FtsJ protein and to a mouse protein possibly involved in embryogenesis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PSMC5NM_002805.6 linkc.178C>T p.Arg60Trp missense_variant Exon 4 of 12 ENST00000310144.11 NP_002796.4 P62195-1A0A140VJS3
PSMC5NM_001199163.2 linkc.154C>T p.Arg52Trp missense_variant Exon 4 of 12 NP_001186092.1 P62195-2
PSMC5XM_047436423.1 linkc.178C>T p.Arg60Trp missense_variant Exon 4 of 8 XP_047292379.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PSMC5ENST00000310144.11 linkc.178C>T p.Arg60Trp missense_variant Exon 4 of 12 1 NM_002805.6 ENSP00000310572.6 P62195-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461814
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jan 16, 2024
Clinical Genetics Laboratory, Skane University Hospital Lund
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.64
D;T;T;T;T;.;.;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
1.0
D;D;D;D;D;.;D;.
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.71
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Pathogenic
3.7
H;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-5.6
D;.;.;.;.;.;D;.
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D;.;.;.;.;.;D;.
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;.;.;.;.
Vest4
0.73
MutPred
0.45
Loss of disorder (P = 2e-04);.;Loss of disorder (P = 2e-04);.;.;.;.;.;
MVP
0.59
MPC
2.5
ClinPred
1.0
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.62
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61907223; COSMIC: COSV56740051; COSMIC: COSV56740051; API