chr17-67342251-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002816.5(PSMD12):āc.1096A>Gā(p.Met366Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PSMD12
NM_002816.5 missense
NM_002816.5 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
PSMD12 (HGNC:9557): (proteasome 26S subunit, non-ATPase 12) 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. A pseudogene has been identified on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMD12 | NM_002816.5 | c.1096A>G | p.Met366Val | missense_variant | 10/11 | ENST00000356126.8 | |
PSMD12 | NM_174871.4 | c.1036A>G | p.Met346Val | missense_variant | 9/10 | ||
PSMD12 | NM_001316341.2 | c.919A>G | p.Met307Val | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMD12 | ENST00000356126.8 | c.1096A>G | p.Met366Val | missense_variant | 10/11 | 1 | NM_002816.5 | P1 | |
PSMD12 | ENST00000584008.5 | c.*1251A>G | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 | 1 | ||||
PSMD12 | ENST00000357146.4 | c.1036A>G | p.Met346Val | missense_variant | 9/10 | 2 | |||
PSMD12 | ENST00000577724.1 | n.234A>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1424614Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 710794
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1424614
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
710794
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Stankiewicz-Isidor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of phosphorylation at T371 (P = 0.1346);.;
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