11-237312-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002817.4(PSMD13):​c.95+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,124 control chromosomes in the GnomAD database, including 48,178 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 0.79 ( 48178 hom., cov: 32)

Consequence

PSMD13
NM_002817.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.493
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSMD13NM_002817.4 linkuse as main transcriptc.95+168T>C intron_variant ENST00000532097.6 NP_002808.3 Q9UNM6-1
PSMD13NM_175932.3 linkuse as main transcriptc.95+168T>C intron_variant NP_787128.2 Q9UNM6-2
PSMD13XM_011520235.4 linkuse as main transcriptc.95+168T>C intron_variant XP_011518537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMD13ENST00000532097.6 linkuse as main transcriptc.95+168T>C intron_variant 1 NM_002817.4 ENSP00000436186.1 Q9UNM6-1

Frequencies

GnomAD3 genomes
AF:
0.793
AC:
120590
AN:
152006
Hom.:
48127
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.884
Gnomad AMI
AF:
0.732
Gnomad AMR
AF:
0.808
Gnomad ASJ
AF:
0.689
Gnomad EAS
AF:
0.827
Gnomad SAS
AF:
0.795
Gnomad FIN
AF:
0.766
Gnomad MID
AF:
0.652
Gnomad NFE
AF:
0.744
Gnomad OTH
AF:
0.760
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.793
AC:
120693
AN:
152124
Hom.:
48178
Cov.:
32
AF XY:
0.796
AC XY:
59189
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.884
Gnomad4 AMR
AF:
0.808
Gnomad4 ASJ
AF:
0.689
Gnomad4 EAS
AF:
0.827
Gnomad4 SAS
AF:
0.795
Gnomad4 FIN
AF:
0.766
Gnomad4 NFE
AF:
0.744
Gnomad4 OTH
AF:
0.756
Alfa
AF:
0.719
Hom.:
2445
Bravo
AF:
0.802
Asia WGS
AF:
0.804
AC:
2798
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
2.3
DANN
Benign
0.46
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3817629; hg19: chr11-237312; COSMIC: COSV61500565; COSMIC: COSV61500565; API