rs3781626

chr11-47421342-T-Achr11-47421342-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002804.5(PSMC3):c.885-615A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,064 control chromosomes in the GnomAD database, including 31,935 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 0.65 (31935 hom., cov: 28)
• Consequence: PSMC3 NM_002804.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC3	NM_002804.5	c.885-615A>T		intron_variant		ENST00000298852.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC3	ENST00000298852.8	c.885-615A>T		intron_variant		1	NM_002804.5

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98228 AN: 150960 Hom.: 31930 Cov.: 28

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.650 AC: 98261 AN: 151064 Hom.: 31935 Cov.: 28 AF XY: 0.652 AC XY: 48027 AN XY: 73716

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.638

Alfa AF: 0.533 Hom.: 1441

Bravo AF: 0.642

Asia WGS AF: 0.684 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.59
Dann	Benign	0.56

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: rs3781626; hg19: chr11-47442893;