chr20-1165492-T-A

Variant names:

• chr20-1165492-T-A
• rs2072965
• NM_006814.5:c.*412T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006814.5(PSMF1):​c.*412T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 867,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

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.*412T>A		3_prime_UTR	Exon 7 of 7	NP_006805.2
	PSMF1	NM_178578.4		c.*412T>A		3_prime_UTR	Exon 8 of 8	NP_848693.2
	PSMF1	NM_001323409.2		c.*458T>A		3_prime_UTR	Exon 7 of 7	NP_001310338.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMF1	ENST00000335877.11	TSL:1 MANE Select	c.*412T>A		3_prime_UTR	Exon 7 of 7	ENSP00000338039.6
	PSMF1	ENST00000333082.7	TSL:1	c.*412T>A		3_prime_UTR	Exon 8 of 8	ENSP00000327704.3
	PSMF1	ENST00000879397.1		c.*412T>A		3_prime_UTR	Exon 8 of 8	ENSP00000549456.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 867610 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 402422

African (AFR) AF: 0.0000592 AC: 1 AN: 16884

American (AMR) AF: 0.00 AC: 0 AN: 3610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6182

East Asian (EAS) AF: 0.00 AC: 0 AN: 4908

South Asian (SAS) AF: 0.00 AC: 0 AN: 19236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 783870

Other (OTH) AF: 0.00 AC: 0 AN: 29326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 40017

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.54

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;