17-63830911-C-T

Variant names:

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

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]

PSMC5 links:

Genome browser will be placed here

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
PSMC5	NM_002805.6 link	c.655C>T	p.Leu219Leu	synonymous_variant	Exon 7 of 12	ENST00000310144.11	NP_002796.4	P62195-1A0A140VJS3
PSMC5	NM_001199163.2 link	c.631C>T	p.Leu211Leu	synonymous_variant	Exon 7 of 12		NP_001186092.1	P62195-2
PSMC5	XM_047436423.1 link	c.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
PSMC5	ENST00000310144.11 link	c.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.:

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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over