20-1168139-A-G

Position:

• chr20-1168139-A-G

Variant summary

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

The NM_006814.5(PSMF1):​c.*3059A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,090 control chromosomes in the GnomAD database, including 16,018 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 0.45 (16017 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PSMF1 NM_006814.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMF1	NM_006814.5	c.*3059A>G		3_prime_UTR_variant	7/7	ENST00000335877.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMF1	ENST00000335877.11	c.*3059A>G		3_prime_UTR_variant	7/7	1	NM_006814.5	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68343 AN: 151966 Hom.: 15989 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.450 AC: 68418 AN: 152084 Hom.: 16017 Cov.: 33 AF XY: 0.452 AC XY: 33644 AN XY: 74364

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.454

Alfa AF: 0.404 Hom.: 25692

Bravo AF: 0.454

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4813044; hg19: chr20-1148783;