Variant rs2293579 details in Genebe, Genetics Data Aggregator

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

Splicing: ADA: 0.0003605

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]

PSMC3 links:

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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
PSMC3	NM_002804.5 linkuse as main transcript	c.1128-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000298852.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PSMC3	ENST00000298852.8 linkuse as main transcript	c.1128-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_002804.5
PSMC3	ENST00000602866.5 linkuse as main transcript	c.1080-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1		P1
PSMC3	ENST00000619920.4 linkuse as main transcript	c.1128-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1
PSMC3	ENST00000530912.5 linkuse as main transcript	c.1002-10C>T	splice_polypyrimidine_tract_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

47013

AN:

151950

Hom.:

8179

Cov.:

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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over