20-1165492-T-C

Position:

• chr20-1165492-T-C

Variant summary

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

The NM_006814.5(PSMF1):​c.*412T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,019,528 control chromosomes in the GnomAD database, including 63,339 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 (8531 hom., cov: 32)
  • Exomes 𝑓: 0.35 (54808 hom.)
• Consequence: PSMF1 NM_006814.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

Genes affected

PSMF1 (HGNC:9571): (proteasome inhibitor subunit 1) 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 a protein that inhibits the activation of the proteasome by the 11S and 19S regulators. Alternative transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

PSMF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMF1	NM_006814.5	c.*412T>C		3_prime_UTR_variant	7/7	ENST00000335877.11	NP_006805.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMF1	ENST00000335877.11	c.*412T>C		3_prime_UTR_variant	7/7	1	NM_006814.5	ENSP00000338039.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47431 AN: 152074 Hom.: 8531 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.352 AC: 304950 AN: 867336 Hom.: 54808 Cov.: 30 AF XY: 0.352 AC XY: 141546 AN XY: 402274

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.312 AC: 47430 AN: 152192 Hom.: 8531 Cov.: 32 AF XY: 0.315 AC XY: 23461 AN XY: 74410

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.323

Alfa AF: 0.355 Hom.: 19852

Bravo AF: 0.305

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.8
DANN	Benign	0.78

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: rs2072965; hg19: chr20-1146136; COSMIC: COSV55672604; COSMIC: COSV55672604;