rs6040222

Positions:

• chr20-1160083-A-G
• chr20-1160083-A-T

Variant summary

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

The NM_006814.5(PSMF1):​c.552-3047A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,800 control chromosomes in the GnomAD database, including 8,557 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 0.33 (8557 hom., cov: 30)
• Consequence: PSMF1 NM_006814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMF1	NM_006814.5	c.552-3047A>G		intron_variant		ENST00000335877.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMF1	ENST00000335877.11	c.552-3047A>G		intron_variant		1	NM_006814.5	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49406 AN: 151682 Hom.: 8557 Cov.: 30

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.326 AC: 49420 AN: 151800 Hom.: 8557 Cov.: 30 AF XY: 0.329 AC XY: 24417 AN XY: 74192

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.344

Alfa AF: 0.307 Hom.: 10651

Bravo AF: 0.322

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.42

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: rs6040222; hg19: chr20-1140727;