20-1154256-T-C

Variant names:

• chr20-1154256-T-C
• rs2300186
• NM_006814.5:c.552-8874T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006814.5(PSMF1):​c.552-8874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,170 control chromosomes in the GnomAD database, including 8,598 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 0.31 (8598 hom., cov: 32)
• Consequence: PSMF1 NM_006814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 4 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMF1	NM_006814.5	c.552-8874T>C		intron_variant	Intron 4 of 6	ENST00000335877.11	NP_006805.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMF1	ENST00000335877.11	c.552-8874T>C		intron_variant	Intron 4 of 6	1	NM_006814.5	ENSP00000338039.6

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47925 AN: 152052 Hom.: 8601 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.315 AC: 47924 AN: 152170 Hom.: 8598 Cov.: 32 AF XY: 0.318 AC XY: 23673 AN XY: 74400

African (AFR) AF: 0.163 AC: 6780 AN: 41534

American (AMR) AF: 0.358 AC: 5476 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3437 AN: 5174

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3618 AN: 10582

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24278 AN: 67974

Other (OTH) AF: 0.328 AC: 693 AN: 2114

Alfa AF: 0.339 Hom.: 1241

Bravo AF: 0.308

Asia WGS AF: 0.471 AC: 1636 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		1.3
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: rs2300186; hg19: chr20-1134900;