NM_006814.5:c.552-8361T>C

Variant names:

• chr20-1154769-T-C
• rs2300185
• NM_006814.5:c.552-8361T>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.552-8361T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,058 control chromosomes in the GnomAD database, including 14,239 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 0.43 (14239 hom., cov: 32)
• Consequence: PSMF1 NM_006814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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.552-8361T>C		intron	N/A	NP_006805.2
	PSMF1	NM_178578.4		c.552-8361T>C		intron	N/A	NP_848693.2
	PSMF1	NM_001323408.2		c.552-8361T>C		intron	N/A	NP_001310337.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.552-8361T>C		intron	N/A	ENSP00000338039.6
	PSMF1	ENST00000333082.7	TSL:1	c.552-8361T>C		intron	N/A	ENSP00000327704.3
	PSMF1	ENST00000879397.1		c.683+2269T>C		intron	N/A	ENSP00000549456.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64794 AN: 151940 Hom.: 14217 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.427 AC: 64856 AN: 152058 Hom.: 14239 Cov.: 32 AF XY: 0.430 AC XY: 31961 AN XY: 74328

African (AFR) AF: 0.472 AC: 19574 AN: 41452

American (AMR) AF: 0.413 AC: 6307 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3692 AN: 5174

South Asian (SAS) AF: 0.463 AC: 2232 AN: 4824

European-Finnish (FIN) AF: 0.393 AC: 4153 AN: 10576

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26121 AN: 67958

Other (OTH) AF: 0.435 AC: 918 AN: 2112

Alfa AF: 0.417 Hom.: 5077

Bravo AF: 0.428

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.65
PhyloP100		-1.6
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: rs2300185; hg19: chr20-1135413;