17-63830911-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002805.6(PSMC5):​c.655C>T​(p.Leu219Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,613,114 control chromosomes in the GnomAD database, including 329,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38698 hom., cov: 29)
Exomes 𝑓: 0.63 ( 290724 hom. )

Consequence

PSMC5
NM_002805.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00700
Variant links:
Genes affected
PSMC5 (HGNC:9552): (proteasome 26S subunit, ATPase 5) 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 one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 17-63830911-C-T is Benign according to our data. Variant chr17-63830911-C-T is described in ClinVar as [Benign]. Clinvar id is 672382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.007 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PSMC5NM_002805.6 linkc.655C>T p.Leu219Leu synonymous_variant Exon 7 of 12 ENST00000310144.11 NP_002796.4 P62195-1A0A140VJS3
PSMC5NM_001199163.2 linkc.631C>T p.Leu211Leu synonymous_variant Exon 7 of 12 NP_001186092.1 P62195-2
PSMC5XM_047436423.1 linkc.655C>T p.Leu219Leu synonymous_variant Exon 7 of 8 XP_047292379.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PSMC5ENST00000310144.11 linkc.655C>T p.Leu219Leu synonymous_variant Exon 7 of 12 1 NM_002805.6 ENSP00000310572.6 P62195-1

Frequencies

GnomAD3 genomes
AF:
0.700
AC:
106235
AN:
151658
Hom.:
38638
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.918
Gnomad AMI
AF:
0.481
Gnomad AMR
AF:
0.636
Gnomad ASJ
AF:
0.544
Gnomad EAS
AF:
0.577
Gnomad SAS
AF:
0.749
Gnomad FIN
AF:
0.644
Gnomad MID
AF:
0.631
Gnomad NFE
AF:
0.610
Gnomad OTH
AF:
0.661
GnomAD3 exomes
AF:
0.649
AC:
163060
AN:
251334
Hom.:
54100
AF XY:
0.647
AC XY:
87859
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.929
Gnomad AMR exome
AF:
0.627
Gnomad ASJ exome
AF:
0.520
Gnomad EAS exome
AF:
0.572
Gnomad SAS exome
AF:
0.737
Gnomad FIN exome
AF:
0.652
Gnomad NFE exome
AF:
0.616
Gnomad OTH exome
AF:
0.622
GnomAD4 exome
AF:
0.627
AC:
916891
AN:
1461338
Hom.:
290724
Cov.:
65
AF XY:
0.629
AC XY:
457163
AN XY:
726984
show subpopulations
Gnomad4 AFR exome
AF:
0.931
Gnomad4 AMR exome
AF:
0.630
Gnomad4 ASJ exome
AF:
0.525
Gnomad4 EAS exome
AF:
0.594
Gnomad4 SAS exome
AF:
0.736
Gnomad4 FIN exome
AF:
0.650
Gnomad4 NFE exome
AF:
0.612
Gnomad4 OTH exome
AF:
0.628
GnomAD4 genome
AF:
0.701
AC:
106352
AN:
151776
Hom.:
38698
Cov.:
29
AF XY:
0.701
AC XY:
51972
AN XY:
74126
show subpopulations
Gnomad4 AFR
AF:
0.918
Gnomad4 AMR
AF:
0.636
Gnomad4 ASJ
AF:
0.544
Gnomad4 EAS
AF:
0.578
Gnomad4 SAS
AF:
0.748
Gnomad4 FIN
AF:
0.644
Gnomad4 NFE
AF:
0.610
Gnomad4 OTH
AF:
0.660
Alfa
AF:
0.636
Hom.:
24951
Bravo
AF:
0.705
Asia WGS
AF:
0.686
AC:
2383
AN:
3478
EpiCase
AF:
0.600
EpiControl
AF:
0.594

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 14, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
4.9
DANN
Benign
0.84

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: rs968719; hg19: chr17-61908271; COSMIC: COSV56742365; COSMIC: COSV56742365; API