20-1165492-T-C

Variant names:

• chr20-1165492-T-C
• rs2072965
• NM_006814.5:c.*412T>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.*412T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,019,528 control chromosomes in the GnomAD database, including 63,339 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 (8531 hom., cov: 32)
  • Exomes 𝑓: 0.35 (54808 hom.)
• Consequence: PSMF1 NM_006814.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 8 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	NM_006814.5	MANE Select	c.*412T>C		3_prime_UTR	Exon 7 of 7	NP_006805.2
	PSMF1	NM_178578.4		c.*412T>C		3_prime_UTR	Exon 8 of 8	NP_848693.2
	PSMF1	NM_001323409.2		c.*458T>C		3_prime_UTR	Exon 7 of 7	NP_001310338.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.*412T>C		3_prime_UTR	Exon 7 of 7	ENSP00000338039.6
	PSMF1	ENST00000333082.7	TSL:1	c.*412T>C		3_prime_UTR	Exon 8 of 8	ENSP00000327704.3
	PSMF1	ENST00000484891.1	TSL:2	n.1144T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47431 AN: 152074 Hom.: 8531 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.352 AC: 304950 AN: 867336 Hom.: 54808 Cov.: 30 AF XY: 0.352 AC XY: 141546 AN XY: 402274

African (AFR) AF: 0.125 AC: 2103 AN: 16880

American (AMR) AF: 0.354 AC: 1273 AN: 3598

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 2447 AN: 6182

East Asian (EAS) AF: 0.656 AC: 3214 AN: 4900

South Asian (SAS) AF: 0.384 AC: 7391 AN: 19230

European-Finnish (FIN) AF: 0.352 AC: 644 AN: 1828

Middle Eastern (MID) AF: 0.363 AC: 639 AN: 1762

European-Non Finnish (NFE) AF: 0.353 AC: 276476 AN: 783642

Other (OTH) AF: 0.367 AC: 10763 AN: 29314

GnomAD4 genome AF: 0.312 AC: 47430 AN: 152192 Hom.: 8531 Cov.: 32 AF XY: 0.315 AC XY: 23461 AN XY: 74410

African (AFR) AF: 0.151 AC: 6276 AN: 41544

American (AMR) AF: 0.358 AC: 5465 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3428 AN: 5174

South Asian (SAS) AF: 0.393 AC: 1894 AN: 4824

European-Finnish (FIN) AF: 0.342 AC: 3627 AN: 10596

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24295 AN: 67986

Other (OTH) AF: 0.323 AC: 681 AN: 2110

Alfa AF: 0.348 Hom.: 40017

Bravo AF: 0.305

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		0.54
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: rs2072965; hg19: chr20-1146136; COSMIC: COSV55672604; COSMIC: COSV55672604;