chr20-1168139-A-G

Variant names:

• chr20-1168139-A-G
• rs4813044
• NM_006814.5:c.*3059A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006814.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	NM_006814.5	MANE Select	c.*3059A>G		3_prime_UTR	Exon 7 of 7	NP_006805.2
	PSMF1	NM_178578.4		c.*3059A>G		3_prime_UTR	Exon 8 of 8	NP_848693.2
	PSMF1	NM_001323408.2		c.*1885A>G		3_prime_UTR	Exon 7 of 7	NP_001310337.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.*3059A>G		3_prime_UTR	Exon 7 of 7	ENSP00000338039.6
	PSMF1	ENST00000484891.1	TSL:2	n.3791A>G		non_coding_transcript_exon	Exon 4 of 4
	PSMF1	ENST00000381898.5	TSL:3	c.242+3663A>G		intron	N/A	ENSP00000371323.5

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.545 AC: 22590 AN: 41448

American (AMR) AF: 0.425 AC: 6498 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3805 AN: 5178

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4822

European-Finnish (FIN) AF: 0.393 AC: 4162 AN: 10584

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26204 AN: 67978

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.412 Hom.: 42185

Bravo AF: 0.454

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.58
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4813044; hg19: chr20-1148783;