Variant 11-237030-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002817.4(PSMD13):c.-20C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,593,610 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0071 ( 1 hom., cov: 34)

Exomes 𝑓: 0.011 ( 129 hom. )

Consequence

PSMD13
NM_002817.4 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.221

Variant links:

Genes affected

PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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 non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PSMD13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-237030-C-T is Benign according to our data. Variant chr11-237030-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038876.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PSMD13	NM_002817.4 linkuse as main transcript	c.-20C>T	5_prime_UTR_variant	1/13	ENST00000532097.6
PSMD13	NM_175932.3 linkuse as main transcript	c.-20C>T	5_prime_UTR_variant	1/11
PSMD13	XM_011520235.4 linkuse as main transcript	c.-20C>T	5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD13	ENST00000532097.6 linkuse as main transcript	c.-20C>T		5_prime_UTR_variant	1/13	1	NM_002817.4	P1	Q9UNM6-1

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.00668

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00757

AC:

1875

AN:

247628

Hom.:

AF XY:

0.00781

AC XY:

1048

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00640

Gnomad FIN exome

AF:

0.00929

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00812

GnomAD4 exome

AF:

0.0113

AC:

16259

AN:

1441244

Hom.:

129

Cov.:

AF XY:

0.0111

AC XY:

7977

AN XY:

718386

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00245

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00675

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.00805

GnomAD4 genome

AF:

0.00714

AC:

1088

AN:

152366

Hom.:

Cov.:

AF XY:

0.00713

AC XY:

531

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00668

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00982

Hom.:

Bravo

AF:

0.00682

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSMD13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.3

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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