rs10838708

Positions:

• chr11-47419962-G-A

Variant summary

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

The NM_002804.5(PSMC3):​c.1127+302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,976 control chromosomes in the GnomAD database, including 12,358 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 0.39 (12358 hom., cov: 31)
• Consequence: PSMC3 NM_002804.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMC3	NM_002804.5	c.1127+302C>T		intron_variant		ENST00000298852.8	NP_002795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMC3	ENST00000298852.8	c.1127+302C>T		intron_variant		1	NM_002804.5	ENSP00000298852.3
PSMC3	ENST00000619920.4	c.1127+302C>T		intron_variant		1		ENSP00000481029.1
PSMC3	ENST00000602866.5	c.1079+302C>T		intron_variant		1		ENSP00000473652.1
PSMC3	ENST00000530912.5	c.1001+302C>T		intron_variant		5		ENSP00000433097.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58759 AN: 151860 Hom.: 12347 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.387 AC: 58798 AN: 151976 Hom.: 12358 Cov.: 31 AF XY: 0.384 AC XY: 28535 AN XY: 74252

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.423

Alfa AF: 0.456 Hom.: 21721

Bravo AF: 0.382

Asia WGS AF: 0.311 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.41

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: rs10838708; hg19: chr11-47441513;