20-1120026-A-G

Position:

• chr20-1120026-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.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

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 (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMF1	NM_006814.5	c.129+1124A>G		intron_variant		ENST00000335877.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMF1	ENST00000335877.11	c.129+1124A>G		intron_variant		1	NM_006814.5	P1

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.0620

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.113

Alfa AF: 0.106 Hom.: 445

Bravo AF: 0.122

Asia WGS AF: 0.0500 AC: 175 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	5.1
DANN	Benign	0.64

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: rs3787573; hg19: chr20-1100669;