chr17-63830911-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

38 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.655C>T	p.Leu219Leu	synonymous	Exon 7 of 12	NP_002796.4
	PSMC5	NM_001199163.2		c.631C>T	p.Leu211Leu	synonymous	Exon 7 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.655C>T	p.Leu219Leu	synonymous	Exon 7 of 12	ENSP00000310572.6	P62195-1
PSMC5	ENST00000961598.1		c.649C>T	p.Leu217Leu	synonymous	Exon 7 of 12	ENSP00000631657.1
PSMC5	ENST00000935074.1		c.655C>T	p.Leu219Leu	synonymous	Exon 7 of 12	ENSP00000605133.1

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

GnomAD2 exomes

AF:

0.649

AC:

163060

AN:

251334

AF XY:

0.647

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 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

African (AFR)

AF:

0.931

AC:

31147

AN:

33472

American (AMR)

AF:

0.630

AC:

28185

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

13716

AN:

26134

East Asian (EAS)

AF:

0.594

AC:

23587

AN:

39700

South Asian (SAS)

AF:

0.736

AC:

63468

AN:

86250

European-Finnish (FIN)

AF:

0.650

AC:

34713

AN:

53400

Middle Eastern (MID)

AF:

0.610

AC:

3521

AN:

5768

European-Non Finnish (NFE)

AF:

0.612

AC:

680626

AN:

1111518

Other (OTH)

AF:

0.628

AC:

37928

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

19542

39084

58627

78169

97711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18470

36940

55410

73880

92350

<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:

0.701

AC:

106352

AN:

151776

Hom.:

38698

Cov.:

AF XY:

0.701

AC XY:

51972

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.918

AC:

38037

AN:

41434

American (AMR)

AF:

0.636

AC:

9700

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1889

AN:

3470

East Asian (EAS)

AF:

0.578

AC:

2959

AN:

5122

South Asian (SAS)

AF:

0.748

AC:

3585

AN:

4792

European-Finnish (FIN)

AF:

0.644

AC:

6775

AN:

10514

Middle Eastern (MID)

AF:

0.651

AC:

190

AN:

292

European-Non Finnish (NFE)

AF:

0.610

AC:

41399

AN:

67894

Other (OTH)

AF:

0.660

AC:

1380

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1474

2949

4423

5898

7372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.641

Hom.:

37480

Bravo

AF:

0.705

Asia WGS

AF:

0.686

AC:

2383

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.594

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

-0.52

CADD

Benign

4.9

(source)

DANN

Benign

0.84

PhyloP100

-0.0070

Mutation Taster

=100/0

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