11-252231-C-G

Variant names:

• chr11-252231-C-G
• rs3817630
• NM_002817.4:c.1036-274C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002817.4(PSMD13):​c.1036-274C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 512,578 control chromosomes in the GnomAD database, including 16,363 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 0.25 (4769 hom., cov: 32)
  • Exomes 𝑓: 0.25 (11594 hom.)
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD13	NM_002817.4	MANE Select	c.1036-274C>G		intron	N/A	NP_002808.3
	PSMD13	NM_175932.3		c.1042-274C>G		intron	N/A	NP_787128.2	Q9UNM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD13	ENST00000532097.6	TSL:1 MANE Select	c.1036-274C>G		intron	N/A	ENSP00000436186.1	Q9UNM6-1
	PSMD13	ENST00000382671.8	TSL:1	n.*782-274C>G		intron	N/A	ENSP00000372117.4	F8W8J6
	PSMD13	ENST00000431206.6	TSL:2	c.1042-274C>G		intron	N/A	ENSP00000396937.2	Q9UNM6-2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37622 AN: 152002 Hom.: 4767 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.246 AC: 88736 AN: 360458 Hom.: 11594 Cov.: 3 AF XY: 0.243 AC XY: 45771 AN XY: 188534

African (AFR) AF: 0.206 AC: 2263 AN: 11000

American (AMR) AF: 0.290 AC: 4449 AN: 15340

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 3258 AN: 11566

East Asian (EAS) AF: 0.184 AC: 4690 AN: 25420

South Asian (SAS) AF: 0.171 AC: 6216 AN: 36332

European-Finnish (FIN) AF: 0.186 AC: 4084 AN: 21950

Middle Eastern (MID) AF: 0.272 AC: 437 AN: 1604

European-Non Finnish (NFE) AF: 0.268 AC: 57874 AN: 215902

Other (OTH) AF: 0.256 AC: 5465 AN: 21344

GnomAD4 genome AF: 0.247 AC: 37637 AN: 152120 Hom.: 4769 Cov.: 32 AF XY: 0.243 AC XY: 18081 AN XY: 74362

African (AFR) AF: 0.204 AC: 8451 AN: 41486

American (AMR) AF: 0.318 AC: 4859 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5178

South Asian (SAS) AF: 0.166 AC: 799 AN: 4820

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10574

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18452 AN: 67982

Other (OTH) AF: 0.271 AC: 572 AN: 2110

Alfa AF: 0.251 Hom.: 609

Bravo AF: 0.257

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.62
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3817630; hg19: chr11-252231;