11-237030-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (1 hom., cov: 34)
  • Exomes 𝑓: 0.011 (129 hom.)
• Consequence: PSMD13 NM_002817.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221

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]

ACMG classification

Verdict is Benign. Variant got -10 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 criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 12 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00715 AC: 1088 AN: 152248 Hom.: 1 Cov.: 34

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.: 12 AF XY: 0.00781 AC XY: 1048 AN XY: 134180

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.: 27 AF XY: 0.0111 AC XY: 7977 AN XY: 718386

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.: 1 Cov.: 34 AF XY: 0.00713 AC XY: 531 AN XY: 74514

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.: 2

Bravo AF: 0.00682

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PSMD13-related disorder Benign:1

Likely benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs12293349; hg19: chr11-237030; COSMIC: COSV61500474; COSMIC: COSV61500474;