chr17-63831196-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002805.6(PSMC5):c.840C>T(p.Leu280Leu) 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0630

Publications

35 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P, Ambry Genetics

PSMC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 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 VariationId is 1239929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002805.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMC5	NM_002805.6	MANE Select	c.840C>T	p.Leu280Leu	synonymous	Exon 8 of 12	NP_002796.4
	PSMC5	NM_001199163.2		c.816C>T	p.Leu272Leu	synonymous	Exon 8 of 12	NP_001186092.1	P62195-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMC5	ENST00000310144.11	TSL:1 MANE Select	c.840C>T	p.Leu280Leu	synonymous	Exon 8 of 12	ENSP00000310572.6	P62195-1
PSMC5	ENST00000961598.1		c.834C>T	p.Leu278Leu	synonymous	Exon 8 of 12	ENSP00000631657.1
PSMC5	ENST00000935074.1		c.840C>T	p.Leu280Leu	synonymous	Exon 8 of 12	ENSP00000605133.1

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

GnomAD2 exomes

AF:

0.380

AC:

80520

AN:

211904

AF XY:

0.385

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 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

African (AFR)

AF:

0.206

AC:

6524

AN:

31688

American (AMR)

AF:

0.404

AC:

15183

AN:

37550

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

5487

AN:

22454

East Asian (EAS)

AF:

0.543

AC:

21264

AN:

39140

South Asian (SAS)

AF:

0.552

AC:

43241

AN:

78310

European-Finnish (FIN)

AF:

0.424

AC:

21925

AN:

51650

Middle Eastern (MID)

AF:

0.305

AC:

1668

AN:

5476

European-Non Finnish (NFE)

AF:

0.327

AC:

354269

AN:

1083168

Other (OTH)

AF:

0.352

AC:

20368

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19238

38477

57715

76954

96192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11998

23996

35994

47992

59990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.318

AC:

48235

AN:

151702

Hom.:

8375

Cov.:

AF XY:

0.328

AC XY:

24337

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.208

AC:

8613

AN:

41366

American (AMR)

AF:

0.385

AC:

5880

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3468

East Asian (EAS)

AF:

0.520

AC:

2661

AN:

5120

South Asian (SAS)

AF:

0.575

AC:

2740

AN:

4764

European-Finnish (FIN)

AF:

0.436

AC:

4594

AN:

10530

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21908

AN:

67890

Other (OTH)

AF:

0.312

AC:

657

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1601

3202

4804

6405

8006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.322

Hom.:

35933

Bravo

AF:

0.305

Asia WGS

AF:

0.524

AC:

1819

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

(source)

DANN

Benign

0.89

PhyloP100

-0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over