20-1120026-A-G

Variant names:

• chr20-1120026-A-G
• rs3787573
• NM_006814.5:c.129+1124A>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.129+1124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,036 control chromosomes in the GnomAD database, including 1,183 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 0.12 (1183 hom., cov: 31)
• Consequence: PSMF1 NM_006814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.161 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	NM_006814.5	MANE Select	c.129+1124A>G		intron	N/A	NP_006805.2	Q92530
	PSMF1	NM_178578.4		c.129+1124A>G		intron	N/A	NP_848693.2	Q92530
	PSMF1	NM_001323408.2		c.129+1124A>G		intron	N/A	NP_001310337.1	Q5QPM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.129+1124A>G		intron	N/A	ENSP00000338039.6	Q92530
	PSMF1	ENST00000333082.7	TSL:1	c.129+1124A>G		intron	N/A	ENSP00000327704.3	Q92530
	PSMF1	ENST00000879397.1		c.129+1124A>G		intron	N/A	ENSP00000549456.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17916 AN: 151918 Hom.: 1182 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.0179

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.118 AC: 17931 AN: 152036 Hom.: 1183 Cov.: 31 AF XY: 0.114 AC XY: 8455 AN XY: 74310

African (AFR) AF: 0.164 AC: 6794 AN: 41434

American (AMR) AF: 0.105 AC: 1607 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5174

South Asian (SAS) AF: 0.0179 AC: 86 AN: 4810

European-Finnish (FIN) AF: 0.0918 AC: 970 AN: 10570

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7700 AN: 67982

Other (OTH) AF: 0.113 AC: 239 AN: 2106

Alfa AF: 0.108 Hom.: 500

Bravo AF: 0.122

Asia WGS AF: 0.0500 AC: 175 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	5.1
DANN	Benign	0.64
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3787573; hg19: chr20-1100669;