rs939915

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.489

Publications

11 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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
PSMD13NM_002817.4 linkc.95+593T>A intron_variant Intron 1 of 12 ENST00000532097.6 NP_002808.3 Q9UNM6-1
PSMD13NM_175932.3 linkc.95+593T>A intron_variant Intron 1 of 10 NP_787128.2 Q9UNM6-2
PSMD13XM_011520235.4 linkc.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
PSMD13ENST00000532097.6 linkc.95+593T>A intron_variant Intron 1 of 12 1 NM_002817.4 ENSP00000436186.1 Q9UNM6-1

Frequencies

GnomAD3 genomes
AF:
0.160
AC:
24401
AN:
152110
Hom.:
2490
Cov.:
33
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1025
2049
3074
4098
5123
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
256
512
768
1024
1280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Publications

Other links and lift over

dbSNP: rs939915; hg19: chr11-237737; API