Variant chr17-63831196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_002805.6(PSMC5):c.840C>T(p.Leu280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,558,958 control chromosomes in the GnomAD database, including 97,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8375 hom., cov: 30)

Exomes 𝑓: 0.35 ( 89475 hom. )

Consequence

PSMC5
NM_002805.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0630

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-63831196-C-T is Benign according to our data. Variant chr17-63831196-C-T is described in ClinVar as [Benign]. Clinvar id is 1239929.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.063 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PSMC5	NM_002805.6 linkuse as main transcript	c.840C>T	p.Leu280=	synonymous_variant	8/12	ENST00000310144.11
PSMC5	NM_001199163.2 linkuse as main transcript	c.816C>T	p.Leu272=	synonymous_variant	8/12
PSMC5	XM_047436423.1 linkuse as main transcript	c.*37C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC5	ENST00000310144.11 linkuse as main transcript	c.840C>T	p.Leu280=	synonymous_variant	8/12	1	NM_002805.6	P1	P62195-1

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48206

AN:

151584

Hom.:

8364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.310

GnomAD3 exomes

AF:

0.380

AC:

80520

AN:

211904

Hom.:

16395

AF XY:

0.385

AC XY:

43610

AN XY:

113182

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.432

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.348

AC:

489929

AN:

1407256

Hom.:

89475

Cov.:

AF XY:

0.353

AC XY:

244876

AN XY:

693852

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.318

AC:

48235

AN:

151702

Hom.:

8375

Cov.:

AF XY:

0.328

AC XY:

24337

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.575

Gnomad4 FIN

AF:

0.436

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.321

Hom.:

17213

Bravo

AF:

0.305

Asia WGS

AF:

0.524

AC:

1819

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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