9-120818099-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005047.4(PSMD5):āc.1322T>Cā(p.Val441Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,096 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 (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
PSMD5
NM_005047.4 missense
NM_005047.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 8.94
Genes affected
PSMD5 (HGNC:9563): (proteasome 26S subunit, non-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. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33944178).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSMD5 | NM_005047.4 | c.1322T>C | p.Val441Ala | missense_variant | 10/10 | ENST00000210313.8 | NP_005038.1 | |
PSMD5 | NM_001270427.2 | c.1193T>C | p.Val398Ala | missense_variant | 9/9 | NP_001257356.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSMD5 | ENST00000210313.8 | c.1322T>C | p.Val441Ala | missense_variant | 10/10 | 1 | NM_005047.4 | ENSP00000210313.2 | ||
PSMD5 | ENST00000373904.5 | c.1193T>C | p.Val398Ala | missense_variant | 9/9 | 2 | ENSP00000363011.5 | |||
PSMD5 | ENST00000373920.6 | c.277-2311T>C | intron_variant | 5 | ENSP00000363030.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
3
AN:
152224
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461872Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 exome
AF:
AC:
5
AN:
1461872
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74380
GnomAD4 genome
AF:
AC:
3
AN:
152224
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74380
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 | Jun 17, 2024 | The c.1322T>C (p.V441A) alteration is located in exon 10 (coding exon 10) of the PSMD5 gene. This alteration results from a T to C substitution at nucleotide position 1322, causing the valine (V) at amino acid position 441 to be replaced by an alanine (A). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Loss of sheet (P = 0.0315);.;
MVP
MPC
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