ENST00000527047.5:n.1268A>C

Variant names:

• chr11-248181-A-C
• rs559422
• ENST00000527047.5:n.1268A>C

Variant summary

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

The ENST00000527047.5(PSMD13):​n.1268A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 153,046 control chromosomes in the GnomAD database, including 413 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 0.064 (413 hom., cov: 32)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: PSMD13 ENST00000527047.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527047.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD13	NM_002817.4	MANE Select	c.569-595A>C		intron	N/A	NP_002808.3
	PSMD13	NM_175932.3		c.575-595A>C		intron	N/A	NP_787128.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD13	ENST00000527047.5	TSL:1	n.1268A>C		non_coding_transcript_exon	Exon 6 of 6
	PSMD13	ENST00000532097.6	TSL:1 MANE Select	c.569-595A>C		intron	N/A	ENSP00000436186.1
	PSMD13	ENST00000382671.8	TSL:1	n.*315-595A>C		intron	N/A	ENSP00000372117.4

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9743 AN: 151984 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0607

GnomAD4 exome AF: 0.0572 AC: 54 AN: 944 Hom.: 0 Cov.: 0 AF XY: 0.0587 AC XY: 29 AN XY: 494

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.0221 AC: 3 AN: 136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0303 AC: 2 AN: 66

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0657 AC: 46 AN: 700

Other (OTH) AF: 0.125 AC: 3 AN: 24

GnomAD4 genome AF: 0.0642 AC: 9766 AN: 152102 Hom.: 413 Cov.: 32 AF XY: 0.0637 AC XY: 4732 AN XY: 74336

African (AFR) AF: 0.0275 AC: 1141 AN: 41488

American (AMR) AF: 0.0739 AC: 1129 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3464

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5178

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4824

European-Finnish (FIN) AF: 0.0824 AC: 871 AN: 10564

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5756 AN: 67994

Other (OTH) AF: 0.0624 AC: 132 AN: 2114

Alfa AF: 0.0762 Hom.: 549

Bravo AF: 0.0631

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.73
PhyloP100		-0.77
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: rs559422; hg19: chr11-248181;