chr11-47419207-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002804.5(PSMC3):​c.1128-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,228 control chromosomes in the GnomAD database, including 116,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8182 hom., cov: 32)
Exomes 𝑓: 0.38 ( 107977 hom. )

Consequence

PSMC3
NM_002804.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0003605
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380
Variant links:
Genes affected
PSMC3 (HGNC:9549): (proteasome 26S subunit, ATPase 3) 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 that have chaperone-like activity. This subunit may compete with PSMC2 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. A pseudogene has been identified on chromosome 9. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PSMC3NM_002804.5 linkuse as main transcriptc.1128-10C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000298852.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PSMC3ENST00000298852.8 linkuse as main transcriptc.1128-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_002804.5
PSMC3ENST00000602866.5 linkuse as main transcriptc.1080-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 P1
PSMC3ENST00000619920.4 linkuse as main transcriptc.1128-10C>T splice_polypyrimidine_tract_variant, intron_variant 1
PSMC3ENST00000530912.5 linkuse as main transcriptc.1002-10C>T splice_polypyrimidine_tract_variant, intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.309
AC:
47013
AN:
151950
Hom.:
8179
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.158
Gnomad AMI
AF:
0.319
Gnomad AMR
AF:
0.284
Gnomad ASJ
AF:
0.412
Gnomad EAS
AF:
0.365
Gnomad SAS
AF:
0.477
Gnomad FIN
AF:
0.287
Gnomad MID
AF:
0.310
Gnomad NFE
AF:
0.388
Gnomad OTH
AF:
0.349
GnomAD3 exomes
AF:
0.353
AC:
88425
AN:
250172
Hom.:
16919
AF XY:
0.369
AC XY:
49836
AN XY:
135220
show subpopulations
Gnomad AFR exome
AF:
0.160
Gnomad AMR exome
AF:
0.222
Gnomad ASJ exome
AF:
0.410
Gnomad EAS exome
AF:
0.372
Gnomad SAS exome
AF:
0.488
Gnomad FIN exome
AF:
0.294
Gnomad NFE exome
AF:
0.387
Gnomad OTH exome
AF:
0.368
GnomAD4 exome
AF:
0.379
AC:
553979
AN:
1461160
Hom.:
107977
Cov.:
39
AF XY:
0.383
AC XY:
278614
AN XY:
726932
show subpopulations
Gnomad4 AFR exome
AF:
0.146
Gnomad4 AMR exome
AF:
0.230
Gnomad4 ASJ exome
AF:
0.412
Gnomad4 EAS exome
AF:
0.308
Gnomad4 SAS exome
AF:
0.479
Gnomad4 FIN exome
AF:
0.298
Gnomad4 NFE exome
AF:
0.390
Gnomad4 OTH exome
AF:
0.381
GnomAD4 genome
AF:
0.309
AC:
47021
AN:
152068
Hom.:
8182
Cov.:
32
AF XY:
0.306
AC XY:
22767
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.158
Gnomad4 AMR
AF:
0.284
Gnomad4 ASJ
AF:
0.412
Gnomad4 EAS
AF:
0.365
Gnomad4 SAS
AF:
0.477
Gnomad4 FIN
AF:
0.287
Gnomad4 NFE
AF:
0.388
Gnomad4 OTH
AF:
0.346
Alfa
AF:
0.350
Hom.:
3126
Bravo
AF:
0.299
Asia WGS
AF:
0.411
AC:
1430
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
9.9
DANN
Benign
0.57
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00036
dbscSNV1_RF
Benign
0.0020
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2293579; hg19: chr11-47440758; COSMIC: COSV54080142; COSMIC: COSV54080142; API