11-47422842-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002804.5(PSMC3):c.723C>T(p.Ala241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,611,312 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PSMC3 NM_002804.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.547

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-47422842-G-A is Benign according to our data. Variant chr11-47422842-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.547 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC3	NM_002804.5	c.723C>T	p.Ala241=	synonymous_variant	7/12	ENST00000298852.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC3	ENST00000298852.8	c.723C>T	p.Ala241=	synonymous_variant	7/12	1	NM_002804.5

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152138 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000510 AC: 127 AN: 248934 Hom.: 1 AF XY: 0.000364 AC XY: 49 AN XY: 134562

Gnomad AFR exome AF: 0.00597

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.000306

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000991

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000227 AC: 331 AN: 1459056 Hom.: 0 Cov.: 31 AF XY: 0.000181 AC XY: 131 AN XY: 725670

Gnomad4 AFR exome AF: 0.00602

Gnomad4 AMR exome AF: 0.000360

Gnomad4 ASJ exome AF: 0.000193

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000582

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.0000549

Gnomad4 OTH exome AF: 0.000614

GnomAD4 genome AF: 0.00187 AC: 284 AN: 152256 Hom.: 2 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74444

Gnomad4 AFR AF: 0.00614

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00211

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

PSMC3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	2.7
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs148054958; hg19: chr11-47444393;