rs505404

Positions:

• chr11-243268-T-G

Variant summary

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

The NM_002817.4(PSMD13):​c.175-773T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 438,562 control chromosomes in the GnomAD database, including 14,494 homozygotes. 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: 𝑓 0.27 (6824 hom., cov: 32)
  • Exomes 𝑓: 0.21 (7670 hom.)
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD13	NM_002817.4	c.175-773T>G		intron_variant		ENST00000532097.6
PSMD13	NM_175932.3	c.96-773T>G		intron_variant
PSMD13	XM_011520235.4	c.175-773T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD13	ENST00000532097.6	c.175-773T>G		intron_variant		1	NM_002817.4	P1
	ENST00000620253.1	n.216A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41643 AN: 151980 Hom.: 6811 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00499

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.210 AC: 60237 AN: 286464 Hom.: 7670 Cov.: 0 AF XY: 0.199 AC XY: 32211 AN XY: 162192

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.00200

Gnomad4 SAS exome AF: 0.0862

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.274 AC: 41706 AN: 152098 Hom.: 6824 Cov.: 32 AF XY: 0.272 AC XY: 20223 AN XY: 74354

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00481

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.238

Alfa AF: 0.225 Hom.: 2291

Bravo AF: 0.280

Asia WGS AF: 0.0760 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.7
DANN	Benign	0.43

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: rs505404; hg19: chr11-243268;