20-1118880-T-G

Position:

• chr20-1118880-T-G

Variant summary

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

The NM_006814.5(PSMF1):​c.107T>G​(p.Phe36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,732 control chromosomes in the GnomAD database, including 532,946 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.80 (49459 hom., cov: 33)
  • Exomes 𝑓: 0.81 (483487 hom.)
• Consequence: PSMF1 NM_006814.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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]

PSMF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.395921E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMF1	NM_006814.5	c.107T>G	p.Phe36Cys	missense_variant	1/7	ENST00000335877.11	NP_006805.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMF1	ENST00000335877.11	c.107T>G	p.Phe36Cys	missense_variant	1/7	1	NM_006814.5	ENSP00000338039.6

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122070 AN: 152080 Hom.: 49416 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.789

GnomAD3 exomes AF: 0.782 AC: 195182 AN: 249594 Hom.: 77562 AF XY: 0.784 AC XY: 105933 AN XY: 135036

Gnomad AFR exome AF: 0.815

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.767

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.829

Gnomad OTH exome AF: 0.784

GnomAD4 exome AF: 0.811 AC: 1184745 AN: 1461534 Hom.: 483487 Cov.: 60 AF XY: 0.810 AC XY: 588668 AN XY: 727100

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.768

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.803 AC: 122176 AN: 152198 Hom.: 49459 Cov.: 33 AF XY: 0.797 AC XY: 59298 AN XY: 74410

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.792

Alfa AF: 0.816 Hom.: 129878

Bravo AF: 0.801

TwinsUK AF: 0.823 AC: 3052

ALSPAC AF: 0.828 AC: 3190

ESP6500AA AF: 0.812 AC: 3576

ESP6500EA AF: 0.829 AC: 7131

ExAC AF: 0.785 AC: 95338

Asia WGS AF: 0.648 AC: 2254 AN: 3478

EpiCase AF: 0.827

EpiControl AF: 0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.76
DEOGEN2	Benign	0.0062	T;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.053	T;T;T;.
MetaRNN	Benign	9.4e-7	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;.;.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.030	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.097	T;T;T;T
Sift4G	Uncertain	0.048	D;T;D;D
Polyphen		0.0	B;.;B;B
Vest4		0.091
MPC		0.11
ClinPred		0.0052	T
GERP RS		1.9
Varity_R		0.093
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1803415; hg19: chr20-1099523; COSMIC: COSV55672896; COSMIC: COSV55672896;