chr11-248181-A-C

Position:

• chr11-248181-A-C

Variant summary

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

The NM_002817.4(PSMD13):​c.569-595A>C variant causes a intron 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 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD13	NM_002817.4	c.569-595A>C		intron_variant		ENST00000532097.6
PSMD13	NM_175932.3	c.575-595A>C		intron_variant
PSMD13	XM_011520235.4	c.569-595A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD13	ENST00000532097.6	c.569-595A>C		intron_variant		1	NM_002817.4	P1

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

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0657

Gnomad4 OTH exome AF: 0.125

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

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0739

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0516

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0807 Hom.: 313

Bravo AF: 0.0631

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.73

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: rs559422; hg19: chr11-248181;