rs939915

chr11-237737-T-A

Variant summary

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

The NM_002817.4(PSMD13):c.95+593T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,228 control chromosomes in the GnomAD database, including 2,491 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 0.16 (2491 hom., cov: 33)
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD13	NM_002817.4	c.95+593T>A		intron_variant		ENST00000532097.6
PSMD13	NM_175932.3	c.95+593T>A		intron_variant
PSMD13	XM_011520235.4	c.95+593T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD13	ENST00000532097.6	c.95+593T>A		intron_variant		1	NM_002817.4	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24401 AN: 152110 Hom.: 2490 Cov.: 33

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24415 AN: 152228 Hom.: 2491 Cov.: 33 AF XY: 0.162 AC XY: 12035 AN XY: 74432

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.157

Alfa AF: 0.194 Hom.: 386

Bravo AF: 0.151

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	9.6
Dann	Benign	0.53

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: rs939915; hg19: chr11-237737;