rs34457782

Positions:

chr14-23042370-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2

The NM_001099780.2(PSMB11):c.145G>A(p.Gly49Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 1,613,660 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 52 hom. )

Consequence

PSMB11
NM_001099780.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.96

Variant links:

Genes affected

PSMB11 (HGNC:31963): (proteasome subunit beta 11) Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system. Proteolysis is conducted by 20S proteasomes, complexes of 28 subunits arranged as a cylinder in 4 heteroheptameric rings: alpha-1 to -7, beta-1 to -7, beta-1 to -7, and alpha-1 to -7. The catalytic subunits are beta-1 (PSMB6; MIM 600307), beta-2 (PSMB7; MIM 604030), and beta-5 (PSMB5; MIM 600306). Three additional subunits, beta-1i (PSMB9; MIM 177045), beta-2i (PSMB10; MIM 176847), and beta-5i (PSMB8; MIM 177046), are induced by gamma-interferon (IFNG; MIM 147570) and are preferentially incorporated into proteasomes to make immunoproteasomes. PSMB11, or beta-5t, is a catalytic subunit expressed exclusively in cortical thymic epithelial cells (Murata et al., 2007 [PubMed 17540904]).[supplied by OMIM, Mar 2008]

PSMB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.015518874).

BP6

Variant 14-23042370-G-A is Benign according to our data. Variant chr14-23042370-G-A is described in ClinVar as [Benign]. Clinvar id is 771191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00598 (911/152266) while in subpopulation EAS AF= 0.0274 (142/5174). AF 95% confidence interval is 0.0238. There are 7 homozygotes in gnomad4. There are 435 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB11	NM_001099780.2 linkuse as main transcript	c.145G>A	p.Gly49Ser	missense_variant	1/1	ENST00000408907.5	NP_001093250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB11	ENST00000408907.5 linkuse as main transcript	c.145G>A	p.Gly49Ser	missense_variant	1/1		NM_001099780.2	ENSP00000386212	P1

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

906

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0274

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00691

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00742

AC:

1848

AN:

248998

Hom.:

AF XY:

0.00743

AC XY:

1004

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.0220

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00770

Gnomad OTH exome

AF:

0.00810

GnomAD4 exome

AF:

0.00709

AC:

10359

AN:

1461394

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

5162

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.0256

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.00692

Gnomad4 OTH exome

AF:

0.00696

GnomAD4 genome

AF:

0.00598

AC:

911

AN:

152266

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0274

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00691

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00712

Hom.:

Bravo

AF:

0.00549

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000690

AC:

ESP6500EA

AF:

0.00622

AC:

ExAC

AF:

0.00746

AC:

904

EpiCase

AF:

0.00725

EpiControl

AF:

0.00931

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.36

MutationAssessor

Pathogenic

4.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MVP

0.87

MPC

0.61

ClinPred

0.099

GERP RS

5.4

Varity_R

0.90

gMVP

0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over