rs939915

Variant names:

• chr11-237737-T-A
• rs939915
• NM_002817.4:c.95+593T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.79).
• 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 rank	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.95+593T>A		intron_variant	Intron 1 of 12	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.95+593T>A		intron_variant	Intron 1 of 10		NP_787128.2
PSMD13	XM_011520235.4	c.95+593T>A		intron_variant	Intron 1 of 10		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.95+593T>A		intron_variant	Intron 1 of 12	1	NM_002817.4	ENSP00000436186.1

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

African (AFR) AF: 0.0622 AC: 2586 AN: 41560

American (AMR) AF: 0.174 AC: 2657 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5194

South Asian (SAS) AF: 0.0785 AC: 379 AN: 4830

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10566

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14847 AN: 67994

Other (OTH) AF: 0.157 AC: 332 AN: 2112

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
PhyloP100		0.49
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: rs939915; hg19: chr11-237737;